bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide
Authors: Berry C. , Touyz R. , Dominiczak A. F. , Webb R. C. , Johns D. G.
Published: December 2017

Angiotensin II (ANG II) is a pleiotropic vasoactive peptide that binds to two distinct receptors: the ANG II type 1 (AT1) and type 2 (AT2) receptors. Activation of the renin-angiotensin system (RAS) results in vascular hypertrophy, vasoconstriction, salt and water retention, and hypertension. These effects are mediated predominantly by AT1receptors. Paradoxically, other ANG II-mediated effects, including cell death, vasodilation, and natriuresis, are mediated by AT2receptor activation. Our understanding of ANG II signaling mechanisms remains incomplete. AT1receptor activation triggers a variety of intracellular systems, including tyrosine kinase-induced protein phosphorylation, production of arachidonic acid metabolites, alteration of reactive oxidant species activities, and fluxes in intracellular Ca2+concentrations. AT2receptor activation leads to stimulation of bradykinin, nitric oxide production, and prostaglandin metabolism, which are, in large part, opposite to the effects of the AT1receptor. The signaling pathways of ANG II receptor activation are a focus of intense investigative effort. We critically appraise the literature on the signaling mechanisms whereby AT1and AT2receptors elicit their respective actions. We also consider the recently reported interaction between ANG II and ceramide, a lipid second messenger that mediates cytokine receptor activation. Finally, we discuss the potential physiological cross talk that may be operative between the angiotensin receptor subtypes in relation to health and cardiovascular disease. This may be clinically relevant, inasmuch as inhibitors of the RAS are increasingly used in treatment of hypertension and coronary heart disease, where activation of the RAS is recognized.
Integrin-binding peptides containing RGD produce coronary arteriolar dilation via cyclooxygenase activation
Authors: Hein Travis W. , Platts Steven H. , Waitkus-Edwards Kelli R. , Kuo Lih , Mousa Shaker A. , Meininger Gerald A.
Published: December 2017

Integrin binding by Arg-Gly-Asp (RGD)-containing peptides has been shown to alter vascular tone in a variety of blood vessels and has been implicated as a mechanism of vasoregulation during tissue injury. However, the effect of these peptides in the coronary circulation has not been examined. Thus the purpose of our study was to test the hypothesis that integrins act as receptors linked to the regulation of coronary vasomotor function. In particular, the ability of RGD-containing peptides to influence vascular tone by interacting with the αvβ3- and α5β1-integrins was studied in isolated pig coronary arterioles. All vessels developed basal tone and dilated in a concentration-dependent manner to soluble peptides cyclic GPenGRGDSPCA (cyclic RGD), an αvβ3-cyclic-binding peptide (XJ735), DMP7677, an α5β1-binding peptide, and to protease-generated (neutrophil elastase) fragments of denatured collagen type I (a major RGD-containing extracellular matrix protein). The vasodilations to cyclic RGD, XJ735, and collagen fragments were almost completely blocked by endothelial removal or by the cyclooxygenase inhibitor indomethacin. In contrast, after endothelial removal and incubation with indomethacin, coronary arterioles showed concentration-dependent constriction to the α5β1-integrin ligand DMP7677 but not to cyclic RGD or XJ735. Collectively, our results indicate that activation of endothelial αvβ3- and α5β1-integrins mediates coronary arteriolar dilation via the endothelial production of cyclooxygenase-derived prostaglandins. These data support a role for integrins in the regulation of coronary vascular tone that may be particularly important during myocardial injury.
Postischemic functional recovery in immature hearts is influenced by performance index and assessment technique
Authors: Torrance Shona M. , Wittnich Carin
Published: December 2017

In the in vivo immature heart, conflicting results are reported for postischemic functional recovery. This study determines whether interpretations of functional recovery are influenced by the contractile performance index (systolic pressure, developed pressure, and maximum rate of systolic pressure increase per unit time) reported or the assessment technique (isovolumetric and variable-volume) utilized. In neonatal pigs ( n = 6) on cardiopulmonary bypass, each performance index was examined using both assessment techniques before myocardial ischemia and at 15, 30, and 60 min of reperfusion. With the use of the isovolumetric technique, all performance indexes had significantly different recovery. With the use of the variable-volume assessment technique, recovery of systolic pressure was significantly better than the other indexes. When recovery was compared between the two assessment techniques, systolic pressure recovered significantly better when assessed using the variable-volume technique. For each performance index, the correlation between isovolumetric and variable-volume techniques was positive before ischemia but negative during reperfusion, suggesting that the assessment techniques identified conflicting postischemic contractile performances. Thus both the contractile performance index reported and the assessment technique employed are ultimately important in interpreting postischemic functional recovery in the immature heart.
Altered leptin signaling is sufficient, but not required, for hypotension associated with caloric restriction
Authors: Swoap Steven J.
Published: December 2017

Caloric restriction of mammals leads to decreases in blood pressure and heart rate. Although relevant clinically, the mechanisms involved, in terms of hormones and signaling pathways invoked, are currently not known. Circumstantial evidence suggests that leptin signaling may be involved with the bradycardia and hypotension associated with caloric restriction. This hypothesis was specifically tested using leptin-deficient mice ( ob/ob) or leptin-receptor rats (Koletsky). Ob/ob mice were hypertensive during the light cycle relative to littermate controls (108 ± 2 vs. 100 ± 2 mmHg, respectively). Both ob/ob mice and wild-type mice exhibited hypotension and bradycardia on initiation of a 50% caloric restriction regime, suggesting that the loss of leptin during caloric restriction is not required to explain the cardiovascular effects. Blood pressure in Koletsky rats did not drop in response to caloric restriction during the light cycle, whereas blood pressure in littermate control rats significantly dropped. These data suggest that at least two pathways are involved with cardiovascular effects of caloric restriction: one dependent on leptin signaling and the other independent of the leptin axis.
PR-39 and PR-11 peptides inhibit ischemia-reperfusion injury by blocking proteasome-mediated IκBα degradation
Authors: Bao Jialin , Sato Kaori , Li Min , Gao Youhe , Abid Ruhul , Aird William , Simons Michael , Post Mark J.
Published: December 2017

PR-39 inhibits proteasome-mediated IκBα degradation and might protect against ischemia-reperfusion injury. We studied PR-39, its truncated form PR-11, and a mutant PR-11AAA, which lacks the ability to prevent IκBα degradation, in a rat heart ischemia-reperfusion model. After 30 min of ischemia and 24 h of reperfusion, cardiac function, infarct size, neutrophil infiltration, and myeloperoxidase activity were measured. Intramyocardial injection of 10 nmol/kg PR-39 or PR-11 at the time of reperfusion reduced infarct size by 65% and 57%, respectively, which improved blood pressure, left ventricular systolic pressure, and relaxation and contractility (±dP/d t) compared with vehicle controls 24 h later. Neutrophil infiltration, myeloperoxidase activity, and the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule 1 were reduced. Thus PR-39 and PR-11 effectively inhibit myocardial ischemia-reperfusion injury in the rat in vivo. This effect is mediated by inhibition of IκBα degradation and subsequent inhibition of nuclear factor-κB-dependent adhesion molecules. The active sequence is located in the first 11 amino acids, suggesting a potential for oligopeptide therapy as an adjunct to revascularization.
Role of activated platelets in excitation of cardiac afferents during myocardial ischemia in cats
Authors: Fu Liang-Wu , Longhurst John C.
Published: December 2017

Myocardial ischemia activates cardiac spinal afferents that mediate chest pain and excitatory reflex cardiovascular responses. Platelets are activated during myocardial ischemia and release 5-hydroxytryptamine, which stimulates abdominal spinal afferents. This study investigated the role of activated platelets in excitation of cardiac spinal afferents during ischemia. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from cats and incubated with collagen (2 mg/ml) or thrombin (5 U/ml). We observed reduction of platelets in PRP indicative of platelet activation by collagen and thrombin, respectively. Activity of single-unit, ischemia-sensitive cardiac spinal afferents was recorded from the left sympathetic chain in anesthetized cats. Injection of 1.5 ml PRP + collagen (activated platelets) into the left atrium (LA) stimulated 12 of 13 cardiac afferents. PRP + saline (nonactivated platelets, LA) and PPP + collagen did not alter activity of these afferents. PRP + thrombin (1.5 ml, LA) stimulated eight of nine other cardiac afferents, whereas PPP + thrombin did not stimulate any of the nine afferents. Antiplatelet immune serum (1 ml/kg iv) significantly decreased circulating platelets as well as neutrophils (polymorphonuclear leukocytes, PMNs) in eight other cats, and in each animal, attenuated the ischemia-related increase in activity of cardiac afferents. Conversely, responses of five separate cardiac afferents to ischemia were not diminished after treatment with anti-PMN immune serum when concentration of circulating platelets was maintained by infusion of donated PRP despite the decrease in circulating PMNs. These data indicate activated platelets stimulate ischemia-sensitive cardiac spinal afferents and contribute to activation of these afferents during ischemia.
Blockade of in vivo VEGF-mediated angiogenesis by antisense gene therapy: role of Flk-1 and Flt-1 receptors
Authors: Marchand Geneviève S. , Noiseux Nicolas , Tanguay Jean-François , Sirois Martin G.
Published: December 2017

Angiogenesis, the formation of new blood vessels from preexisting ones, is a critical component of various pathologies such as tumor progression, rheumatoid arthritis, and retinopathies. Vascular endothelial growth factor (VEGF) is a mitogenic and chimiotactic factor capable of inducing angiogenesis through the activation of its receptors, fetal liver kinase-1 (Flk-1) and fms-like tyrosine kinase-1 (Flt-1), expressed on endothelial cells. The purpose of the present study was to assess if a treatment with antisense (AS) oligonucleotides directed against VEGF receptors Flk-1 or Flt-1 mRNA could prevent VEGF-mediated angiogenesis. With the use of miniosmotic pumps, phosphate-buffered saline, VEGF, or VEGF combined with AS-Flk-1, AS-Flt-1, or AS-scrambled oligonucleotides were released in mouse testis for 14 days. VEGF (1, 2.5, and 5 μg) increased the formation of new capillary blood vessels by 236, 246, and 287%, respectively. The combination of AS-Flk-1 or AS-Flt-1 (200 μg) to VEGF (2.5 μg) reduced by 87 and 85% the formation of new blood vessels, respectively, and the expression of their corresponding proteins. These data demonstrate the therapeutical potential of AS-Flk-1 or AS-Flt-1 to prevent VEGF-mediated angiogenesis in vivo.
Mechanisms of sex differences in rat cardiac myocyte response to β-adrenergic stimulation
Authors: Vizgirda Vida M. , Wahler Gordon M. , Sondgeroth Korie L. , Ziolo Mark T. , Schwertz Dorie W.
Published: December 2017

The purpose of this study was to investigate sex differences in the functional response of isolated rat heart ventricular myocytes to β-adrenergic stimulation and in isoproterenol-stimulated signal transduction. Fractional shortening was measured using a video edge-detection system in control- and isoproterenol-stimulated myocytes that had been isolated from weight-matched rats. Number and affinity of the β-adrenergic receptors and the L-type Ca2+ channel were measured in ventricular cardiac membranes by radioligand binding studies. Control- and isoproterenol-mediated alteration in Ca2+ current density ( I Ca) was determined by patch clamping and cellular cAMP content was determined by radioimmunoassay. Study results demonstrate that female myocytes have higher Ca2+channel density and greater I Ca than male myocytes. However, isoproterenol elicits a greater β-adrenergic receptor-mediated increase cell shortening, I Caand cAMP production in male myocytes. Male myocytes were also found to have a higher β-adrenergic receptor density. These results suggest that cardiac myocytes from male rats have an enhanced response to β-adrenergic stimulation due to augmented β-adrenergic signaling that results in a greater transsarcolemmal Ca2+ influx.
Neural influences on cardiovascular variability: possibilities and pitfalls
Authors: Malpas Simon C.
Published: December 2017

Altered variability in the cardiovascular system is associated with a range of cardiovascular diseases and increased mortality. Because blood pressure and heart rate show distinct low-frequency oscillations that appear to be affected by either vagal or sympathetic activity, it has been hoped that measurement of the strength of these oscillations could be used as an index of autonomic tone and thus form the basis of a diagnostic test. This review focuses on recent research that has examined the fundamental origin of variability associated with respiration and a slow oscillation at 0.1 Hz in the human. A new hypothesis is proposed to account for the slow oscillation in heart rate and blood pressure that incorporates components of the central nervous system, other reflex pathways regulating sympathetic activity, and resonance in the baroreflex control of blood pressure. Whereas it is clear that sympathetic activity and arterial baroreflexes are critical elements in producing cardiovascular variability, there is also evidence that other factors, including the ability of the vasculature to respond to sympathetic activity, appear to play a role in determining the strength of oscillations. Given the potential impact of other nonbaroreflex or nonautonomic pathways in affecting cardiovascular variability, it is proposed that one must use care in relating changes in the strength of an oscillation in blood pressure and heart rate as definitively due to a change in autonomic control.
Transport of l-tyrosine by the small intestine in vitro
Authors: Lin Edmund C. C. , Wilson T. Hastings
Published: December 2017

l-Tyrosine was absorbed against a concentration gradient by sacs of isolated small intestine obtained from several animal species. During absorption the tissue segments accumulated the amino acid to concentrations as high as nine times that in the suspending medium. In the case of the hamster the rate of transport was maximal in the mid portion of the small intestine. Studies on specificity of the transport system showed that l-tyrosine and dl-meta-tyrosine were transported while no activity was observed with d-tyrosine, dl-ortho-tyrosine, and 3,5-diiodo-l-tyrosine. Transport of l-tyrosine was inhibited by l-phenylalanine and l-methionine but not by d-phenylalanine. High tyrosine diet did not alter the rate of the in vitro transport of this amino acid in the rat.
Mechanism of alloxan diabetes inhibition by vasopressor drugs
Authors: Meade Robert C. , Klitgaard Howard M.
Published: December 2017

Pretreatment with epinephrine, norepinephrine or Neo-Synephrine prevented allovan diabetes in rats. If the vasopressor action of these drugs was blocked with phentolamine (Regitine) their ability to prevent diabetes was lost. A mixture of sodium radiophosphate and alloxan demonstrated a reduced rate of absorption at the site of injection in epinephrine-treated rats. If the total alloxan dose was given in small divided doses to normal rats an amount in excess of the usual diabetogenic dose could be given without any hyperglycemic effect. It was concluded that the sparing action of these drugs was the result of peripheral vasoconstriction which decreased the rate of alloxan absorption from the site of injection.
Alimentary, blood and other changes due to feeding MnSO4, MgSO4 and Na2SO4
Authors: Moinuddin Jessie Fischer , Lee Helen Wing-Tsit
Published: December 2017

Rats were fed a basal diet or diets containing extra MnSO4, MgSO4 or Na2SO4 in three experiments. The major effects occurred in the experiment with the highest level of extra sulfates (138 mmoles/kg of feed) as follows. The MgSO4-fed rats ate less feed than the Na2SO4-fed rats. Also, in the MgSO4 group the activity of serum alkaline phosphatase was greater and the cleaned, dried cecum was considerably heavier than in the other groups, and the colon plus rectum was slightly longer than in the basal and MnSO4 groups. The MnSO4-fed rats, compared to rats of the other groups in this experiment, ate less feed, gained less body weight, required more feed per gram of gain, drank more water, voided more urine, showed depigmentation of the labial surfaces of the incisor teeth, had less hemoglobin and serum inorganic phosphorus, and had cleaned, dried stomachs of lighter absolute weight. The erythrocyte count was higher in the MnSO4 group than in the basal or Na2SO4 groups.
Metabolic activity of 3,5-dibromothyronine, 3,5-diiodothyronine and 3,3'-diiodo-5-bromothyronine
Authors: Gemmill Chalmers L.
Published: December 2017

Dibromothyronine in large doses increases the metabolism of thyroidectomized rats and promotes growth comparable to diiodothyronine. However, it did not decrease the ratio of thyroid weight to body weight in the antigoiter test. 3,3'-Diiodo-5-bromothyronine also promotes growth in thyroidectomized rats.
Thyroid function, osteoarthritis and epiphyseal closure in various strains of mice
Authors: Silverstein Emanuel , Sokoloff Leon , Jay George E. , Mickelsen Olaf
Published: December 2017

Thyroid function and osteoarthritis were studied in six inbred and six F1 hybrid strains of mice at 16 months of age. Strains having little osteoarthritis of the knee generally had lower T/S ratios than strains more susceptible to joint disease. No correlation could be established between the PBI or thyroid weight and the joint disease. The data supply no support for believing that endogenous insufficiency of thyroid hormone influences the development of degenerative joint disease in mice. When the present findings on epiphyseal maturation in four strains were supplemented with data from previous ones on the same strains, a positive correlation appeared to exist between the T/S ratios of these strains and the degree of epiphyseal closure of the knees.
A mechanism by which helium increases metabolism in small mammals
Authors: Leon H. A. , Cook S. F.
Published: December 2017

The oxygen consumption of male Long-Evans rats was determined at three different ambient temperatures in air and in an equivalent helium-oxygen mixture. It was found that when the ambient temperature is near the skin temperature of the rat, the effect of helium is insignificant. If the ambient temperature is lowered, helium induces an increased metabolism over air at the same temperature. Since helium has a thermal conductivity about six times greater than nitrogen, it is concluded that the accelerated metabolism is in response to the greater heat loss in the presence of helium and the magnitude of this response is proportional to the thermal gradient between the animal and the environment.
Effect of fasting, epinephrine and glucose and insulin on hepatic uptake of nonesterified fatty acids
Authors: Fine Melwyn B. , Williams Robert H.
Published: December 2017

Catheters placed in the portal and hepatic veins of dogs were maintained in position for 2–4 weeks, and experiments were performed in the unanesthetized state no less than 3 days after the operative procedure. Hepatic uptake of nonesterified fatty acids (NEFA) was determined from the portal-hepatic NEFA difference and the hepatic blood flow. Hepatic NEFA uptake was found to increase with fasting and after administration of epinephrine. It was found to decrease after the administration of glucose and insulin. It was concluded that these factors did not directly influence the liver to alter its NEFA uptake but that the liver responded primarily to the concentration of NEFA in the blood entering it.
Components of the evoked potential in the MES auditory cortex
Authors: Tunturi Archie R.
Published: December 2017

The electrical activity during the potential evoked by a p pulse was analyzed statistically by considering amplitude at each 3-msec. epoch a random variable. The rise in standard deviation during the evoked potential was abolished a) by local cocaine on the cortex, b) by a preceding evoked potential and c) by ischemia. The residual mean positive component, with zero standard deviation, was subtracted from the mean of the evoked potential. This yielded a positive-negative component, with which the spontaneous electrical activity is believed to interact. The evoked potential is thus described as the sum of the three random variables: a) spontaneous electrical activity, b) positive component, and c) positive-negative component, with a covariance term involving the spontaneous electrical activity and the positive-negative component.
Bound sodium in artery wall
Authors: Headings Verle E. , Rondell Paul A. , Bohr David F.
Published: December 2017

Analyses were made of total sodium, potassium and chloride content and of inulin space in dog carotid artery. The Ki/Ko gradient was found to be 125/4. Sodium space calculated from these analyses is larger than total hydration, thus precluding calculation of the Nai/No gradient. It is postulated that the excess sodium is associated with the mucopolysaccharides present in the interstitial spaces of the artery wall media. This associated sodium is readily replaced during 3-minute incubation of the artery wall media in Krebs' solution in which either the hydrogen or the potassium concentration is increased. It appears improbable that the majority of the excess sodium can be attributed to a Donna equilibrium since chloride concentration in the incubated tissue is much greater than that calculated to be required for this equilibrium.
Effect of luteinizing hormone and vasopressin on ovarian ascorbic acid
Authors: McCann S. M. , Taleisnik S.
Published: December 2017

Luteinizing hormone (LH) depleted ovarian ascorbic acid of immature or adult rats pretreated with gonadotrophins, the former animals being more sensitive than the latter. Follicle-stimulating hormone, luteotrophin and adrenocorticotrophin had minimal or o activity in this assay, whereas vasopressin but not oxytocin had appreciable activity. Vasopressin was more active in the adult rats. If the doses were expressed on a weight basis, vasopressin was actually more potent than the LH standard in the adults; however, endogenous vasopressin release did not deplete ovarian ascorbic acid. The activity of both LH and vasopressin was either not affected or affected to the same degree by hypophysectomy. Retrograde injection of vasopressin into the ovarian vein showed that the action of vasopressin was a direct one on the ovary. Vasopressin does not interfere with the assay of LH in body fluids by this technique.
Adrenocortical and medullary effects of glucagon
Authors: Scian Louis F. , Westermann Coenaraad D. , Verdesca Arthur S. , Hilton James G.
Published: December 2017

An isolated, perfused adrenal gland preparation in the dog was used to study the direct effect of glucagon on adrenal secretion of hydrocortisone, epinephrine and norepinephrine. Glucagon was demonstrated to have a marked stimulatory effect on catecholamine secretion while having no effect on hydrocortisone secretion. The physiologic implications of these findings are discussed.
Autoradiographic study of Diodrast-I131 transport in Necturus kidney
Authors: Kinter William B. , Leape Lucian L. , Cohen Jordan J.
Published: December 2017

Renal tubular transport of Diodrast-I131 was studied in Necturus by newly devised autoradiographic methods used in conjuction with classical clearance methods. Clearance measurements on individual animals indicate different types of over-all tubular transport ranging from secretion into tubular urine, heretofore reported in many species, to reabsorption out of tubular urine, so far reported only in Necturus. Diodrast content of tubular urine as disclosed by autoradiography both corroborates clearance data and provides evidence that proximal tubules are the major site of Diodrast transport irrespective of direction. This view is supported by inulin-C14 autoradiographs. In addition, significant amounts of Diodrast were accumulated within proximal tubular cells during all types of transport. With less than 3 mg Diodrast/100 ml arterial plasma, the estimated intracellular concentration ranged from 2 to 19 times that in plasma. At higher plasma levels, tubular transport was overwhelmed and intracellular concentration no longer exceeded that in plasma. These results support a previously formulated theory of simultaneous, bidirectional movement of Diodrast across tubular cells in Necturus kidney.
Role of phospholipids in lymphatic transport of dietary lipids in the dog
Authors: Rampone Alfred J.
Published: December 2017

The phospholipids of lymph have been measured in relation to the total lipid in 16 chronic thoracic duct fistula dogs during the postabsorptive state and following the administration of various lipid types in the diet. It was found that phospholipid transport related linearly to total lipid transport under all conditions studied, including the postabsorptive state. The percentage of lymph lipid transported as phospholipid ranged from 3 to 18% and was independent of the type of lipid fed. Depriving the animals of phospholipid precursors in the diet for as long as 90 days previously failed to alter this relationship or the total quantity of lipid transported. The total quantity of phospholipid which could be considered as having been newly synthesized as a direct result of processes underlying absorption of exogenous (dietary) fats was small and probably insignificant. The conclusion is reached that phospholipids probably do not serve as intermediates in the absorptive process, nor do they constitute important vehicles for fatty acid transport in lymph.
Intestinal transport of l-tryptophan in vitro: inhibition by high concentrations
Authors: Spencer Richard P. , Samiy A. H.
Published: December 2017

At a concentration of 5 x 10–3 m, everted hamster intestinal sacs showed net transport of l-tryptophan from the mucosal to the serosal side, when the concentration was initially equal on the two sides. Thus, l-tryptophan is not an exception to the generalization that such intestinal preparations transport monoamino-monocarboxylic amino acids against a concentration gradient. High concentrations of l-tryptophan inhibit such transport. This may account for previous failure by others to observe l-tryptophan transport against a gradient at an initial concentration of 20 x 10–3 m. Transport of l-tryptophan was greater by sacs from the middle of the small intestine than by those from the ends (this has been previously reported for l-phenylalanine and l-tyrosine). On the basis of this observation and those of mutual inhibition of transport, it is likely that the four aromatic amino acids share at least one common step in their intestinal absorption. Segments of hamster small intestine have been shown to accumulate l-tryptophan, developing a concentration greater than that of the bathing fluid.
Inhibition by surgical procedures and drugs of accelerated growth of salivary glands of rats
Authors: Wells Herbert
Published: December 2017

The increase in weight of the submandibular salivary glands which usually follows amputation of the lower incisor teeth was not observed when amputation was preceded by bilateral injection of ethanol into the pterygomandibular space. Implantation into the incisor pulp canals of cotton pledgets impregnated with ethanol or formalin did not prevent the response to amputation. Although resection of a portion of the inferior alveolar nerve did not alter the response of the glands to amputation in rats with intact teeth, the weight of the glands increased slightly after resection of the nerve alone. The increase in gland weight which follows a single amputation of the teeth did not occur in rats treated with barbital, or with chlorisondamine, a ganglionic blocking agent. An adrenergic blocking agent, Dibenamine, not only blocked the response to amputation of the teeth but resulted in atrophy of the submandibular glands in intact rats. It is concluded that the data support the reflex neurological explanation of the phenomenon previously offered, and that the sympathetic nervous system may be involved not only in the response to amputation of the teeth but in the maintenance of normal gland size and function.
Effects of diet on selected glycolytic enzymes of the rat
Authors: Vaughan David A. , Hannon John P. , Vaughan Lucile N.
Published: December 2017

The activities of selected glycolytic enzymes from the liver and muscle of rats subsisting for 4 and 40 days on carbohydrate-free diets high in fat or protein were compared with enzymes from rats fed high carbohydrate diets. The following changes were noted in liver: high fat—a decrease in phosphorylase, glucokinase, glucose-6-phosphate dehydrogenase and formation of pyruvate from 3-phosphoglycerate with no change in glucose-6-phosphatase; high protein—an increase in phosphorylase and a decrease in glucose-6-phosphatase and glucokinase—the other enzymes were unaffected. These diets had no effect on the activity of the enzymes in muscle, except that the high fat diet depressed muscle glucokinase. Conversely, the activities of muscle phosphorylase and the formation of pyruvate increased with time while the activity of muscle glucose-6-phosphate dehydrogenase decreased. It was concluded that the response of liver glycolytic and oxidative enzymes to carbohydrate removal depended to a large extent upon the nutrient substituted. In muscle, glycolysis was not appreciably affected by dietary manipulations.
In vitro I131 uptake by salivary glands, stomach and placenta
Authors: Maqsood M. , Reineke E. P.
Published: December 2017

Slices of various tissues of the rat were incubated at 37°C for 6 hours in 2 ml of medium containing 0.3 µc carrier-free I131. I131 concentration significantly above that of the medium, and of boiled tissues, was observed in salivary glands and stomach, but not in liver or placenta. I131 uptake by parotid was significantly higher than that of submaxillary and sublingual tissues. Uptake by tissues from the cardiac portion of the stomach was significantly greater than in those from the pyloric portion. Concentration of I131 by salivary glands and stomach slices was reduced by the addition of thiouracil (0.02 mg/ml), KSCN (0.1 mg/ml) or NaCN (0.1 mg/ml) but it was not affected by the addition of TSH (100 µg/ml) to the medium. None of these additives influenced the small I131 uptake found in liver and placenta. I131 uptake by salivary glands and stomach of the mouse, dog and cow was similar to that in the rat, except that there was less difference between the parotid and submaxillary glands.
Metabolism of 2-C14-pyruvate after adrenalectomy
Authors: Winternitz W. W. , Forrest W. G.
Published: December 2017

Normal and adrenalectomized rats were infused with 2 C14-pyruvate for 90 minutes. The carcasses and livers were then analyzed for glycogen, protein and fat. The radioactivity of whole tissue homogenates was also assayed. Normal rats formed a large amount of highly active liver glycogen; the adrenalectomized animals did not. The discrepancy was not accounted for by accumulation of C14 in any of the fractions or organs studied, although slightly increased amounts were found in the expired CO2 and in the blood plasma. It is suggested that increased carbohydrate utilization after adrenalectomy may be secondary to diminished glycogenesis and may occur over all available routes.
Effects of fasting, adrenalectomy and cortisol on bone composition and density
Authors: Lobeck Charles C. , Steinkraus Robert E.
Published: December 2017

Cortical marrow-free bone from white rats was analyzed for water, sodium, calcium and citrate content after fasting for 24 and 120 hours with and without adrenalectomy or cortisol administration. Density of fresh cortical bone from all animals was calculated from determinations of volume made by weighing fragments in air and below the surface of water. The rapidly exchangeable fraction of bone sodium was determined, using radiosodium, in all animals killed at 120 hours. There were no observed changes in the sodium content, its exchangeability, or citrate content of bone with any treatment despite an average decrease in serum sodium of 7 mEq/l. and a twofold increase in serum citrate with adrenalectomy at 120 hours. An unexplained slight increase in bone density occurred in cortisol-treated animals after 120 hours which did not make changes in sodium and citrate content more apparent when calculated on a volume basis. With fasting alone there were no observed differences in bone composition but there was an increase in serum citrate at 120 hours which did not occur in fasted rats given cortisol. It was concluded that the hyponatremia and salt depletion of fasted adult rats subjected to adrenalectomy are not sufficient to cause depletion of bone sodium and that changes in serum citrate concentration associated with alterations in adrenal function do not have a detectable effect on bone citrate content.
The pineal gland and aldosterone
Authors: Wurtman Richard Jay , Altschule Mark D. , Greep Roy O. , Falk John L. , Grave Gilman
Published: December 2017

It has recently been suggested that the canine pineal gland secretes a hormone which stimulates the adrenal cortex to release aldosterone. The following experiments were undertaken to determine what effect pinealectomy or administration of bovine pineal extracts has on certain physiologic variables associated with aldosterone activity in rats: a) the relative size of the zona glomerulosa, compared with total adrenal area, was determined planimetrically in 25 female rats treated with pinealectomy, pineal extracts, or both; b) urinary potassium excretion was measured in 4 pinealectomized and 4 control female rats; c) the elective saline intakes, at concentrations ranging from 0 to 3.0%, were measured in 5 male control rats and in 5 animals given 1.0 ml/day of pineal extract. Pinealectomy or pineal extract had no effect on any of these variables, suggesting that the pineal gland does not regulate aldosterone secretion in the rat.
Evidence for an antithrombotic effect of Dicumarol
Authors: Deykin Daniel , Wessler Stanford , Reimer Stanley M.
Published: December 2017

By the technique of serum-induced thrombosis, the effect of Dicumarol in depressing serum thrombotic accelerator (STA) activity was employed as a measure of the antithrombotic action of this drug in dogs. A significant antithrombotic effect, unassociated with hemorrhage, was achieved at levels of prothrombic activity below 15% of the control values. The antithrombotic effect of Dicumarol, as distinct from the anticoagulant effect, was demonstrable only after a latent period of approximately 1 week or more, unless massive doses of the anticoagulant were administered. No clear-cut correlation was evident between depression of STA activity and depression of any coagulation factor singly or in combination known to be affected by Dicumarol. The data reported in this communication represent the first demonstration that Dicumarol may inhibit in vivo thrombus formation (as distinct from in vitro clot formation) mediated exclusively through activation of the intrinsic clotting system.
Anode break excitation on single Ranvier node of frog nerve
Authors: Ooyama Hiroshi , Wright Ernest B.
Published: December 2017

A quantitative study of anodal break excitation in single frog nerve fibers has been carried out. An applied anodal pulse caused an increase in the critical level of depolarization for excitation. Anode break stimulation was effective only if the anodal pulse was immediately followed by depolarization of the single Ranvier node membrane. This condition can be obtained in three ways: 1) by applying the anodal pulse during a conditioning depolarization voltage, which must be equal to or greater than the threshold value for cathodal stimulation; 2) by applying a pulse of such large amplitude so as to produce membrane breakdown, which results in depolarization by intrinsic local currents; 3) by applying the pulse to a fiber already under the influence of intrinsic depolarization resulting from deterioration or high concentrations of potassium in the external solution. True anode break stimulation can only be produced by an exceedingly strong positive pulse. The membrane breakdown resulting from such a pulse, first reported by Stampfli in 1958, is discussed and a hypothesis is presented explaining the physiological implications of this phenomena.
Irreversible hemorrhagic shock in rats: changes in blood glucose and liver glycogen
Authors: Strawitz J. G. , Hift H. , Ehrhardt A. , Cline D. W.
Published: December 2017

Paired fed and fasted rats were subjected to the standard shock procedure consisting of a combination of tail bleeding and heart puncture with an intervening recovery period of 90 minutes. Mortality rates in the two groups were similar but the survival times were shortened in the fasted group. Following tail bleeding all animals mobilized glucose into the blood stream and developed severe hyperglycemia. In those individuals in either group which ultimately died, the blood sugar levels were further reduced following heart puncture; the rates of glucose loss were inversely proportional to survival time; the results were terminal hypoglycemias and near exhaustion of liver glycogen. In contrast, the survivors in either group, examined 4 hours after heart puncture, were found to be hyperglycemic and engaged in glycogen neogenesis. It is concluded that the ultimate death or survival of an animal in hemorrhagic shock is independent of its initial glucose reserves, but seems somehow to be related to its ability to maintain itself in a hyperglycemic state.
Glucose and sorbose absorption at various levels of rat small intestine
Authors: Baker R. David , Searle Gordon W. , Nunn Arthur S.
Published: December 2017

The passage of glucose and sorbose across the wall at various levels of rat small intestine has been studied in vitro. ‘Uphill’ glucose transport was demonstrated in the jejunum and upper half of the ileum but could not be seen in the terminal quarter of small intestine. Aerobically, in the mid-jejunum glucose absorption from the mucosal solution was about 5.5 times as rapid as in the terminal ileum; the aboral decline in absorptive activity, however, occurred only in the lower half of the small intestine; the upper half absorbed glucose at a nearly constant rate throughout. No aboral decline for rate of glucose transfer into the serosal solution was noticed in the upper three-quarters of small intestine, but in the lower quarter the drop was precipitous. The effects of hypoxia and fluoride poisoning, respectively, on glucose movements were much more severe in the upper than in the lower portions of small intestine. Fluoride (48 mm) completely abolished the absorptive activity gradient for glucose along the small intestine. Sorbose movements were quite similar in rate to the fluoride-inhibited glucose movements.
Placental transfer of I131-insulin in the rhesus monkey
Authors: Josimovich J. B. , Knobil E.
Published: December 2017

Pregnant rhesus monkeys were anesthetized, their uteri were exposed, and the interplacental vessels (fetal circulation) were cannulated without incision of the amnion. This procedure permitted simultaneous sampling of maternal blood, umbilical venous blood and umbilical arterial blood. I131-labeled insulin injected into the material circulation was detected in umbilical venous plasma, within 5 minutes after the injection, by the use of a chromatographic procedure which permits the separation of I131-insulin from other iodinated compounds. The concentration of I131-insulin in fetal plasma did not exceed 20% of that found concurrently in maternal plasma. A marked umbilical arterial-venous difference in I131-insulin concentration was consistently observed. The concentration of iodinated degradation products of I131-insulin was considerably higher in umbilical arterial plasma than in umbilical venous plasma, suggesting rapid degradation of the labeled hormone by the fetus. Conversely, the injection of I131-insulin into the fetal circulation was followed by the appearance of significant quantities of the labeled hormone in the maternal circulation. These experiments lead to the conclusion that insulin can cross the primate placenta.
Influence of ions and dinitrophenol on adrenocortical steroidogenesis
Authors: Rosenfeld George
Published: December 2017

The Na, K, Ca, Mg or PO4 content of an artificial medium, shown to support steroidogenesis as well as homologous blood, was altered individually, and the influence of each ionic change on the biosynthetic function of the perfused calf adrenal investigated under three conditions: a) without ACTH, b) with ACTH and c) with steroid substrates. The effect of dinitrophenol (DNP) was explored under similar conditions. Both ACTH-stimulated and unstimulated glands perfused without Ca exhibited an appreciable decrement in corticoid output without any depletion in metabolic activity. Omission of Mg, K or PO4 ions, and reduction of the Na content from 149 to 125 mEq/l. exerted no significant effect. None of the ionic alterations modified the specific, enzymatic hydroxylation or 3ß-dehydrogenase activities of adrenals perfused with various steroid substrates. Adrenals perfused with a markedly elevated K level (25.0 rather than 3.4 mEq/l.) were not inhibited but instead autonomously responded to it by secreting increased amounts of corticoids. Addition of 10–4 M DNP, with and without ACTH, resulted in a striking suppression of corticoid production without a commensurate metabolic depression, and induced depletions of from 80 to 100% in the ability of exposed glands to perform 11ß-, 17α- and 21-hydroxylation without affecting their transformation of the Δ5-3ß-OH group to Δ4-3-ketone.
Leucine-isoleucine antagonism in the rat
Authors: Spolter Pari D. , Harper A. E.
Published: December 2017

Diets are described containing 5 and 7% of l-leucine which cause severe growth retardation of rats for a period of up to 14 days. These diets are more convenient for a study of the mechanism of the growth depression than the diet containing 3% of l-leucine described previously (i). Appetite was depressed in proportion to leucine concentration of the diet. Growth retardation of rats fed a diet containing 5% of l-leucine was almost completely overcome by the addition of isoleucine and valine, and as little as 0.16% of l-isoleucine + 0.15% of L-valine were as effective as much higher concentrations. The growth-retarding action of an excess of dietary l-leucine has been demonstrated with a diet in which the protein was replaced by an amino acid mixture, suggesting that the site of antagonism is not in some phase of protein digestion. No effect of excess of dietary leucine on the over-all nitrogen absorption, on nitrogen retention, or on the rate of gastric emptying was observed. Injections of insulin counteracted the appetite-depressing effect of excess leucine in some rats. When the food intake of these rats increased, they grew more rapidly indicating that a high intake of leucine per se is not toxic.
Micropuncture study of renal tubular transfer of sodium chloride in the rat
Authors: Windhager Erich E. , Giebisch Gerhard
Published: December 2017

Micropuncture studies were made in the rat on the relationship between net water and net sodium movement across proximal tubular epithelium during strong osmotic diuresis induced by intravenous infusion of a 20% mannitol solution. Results obtained in the mannitol series were compared with data obtained in rats during infusion of 0.9% saline. Collected tubular fluid and appropriate plasma samples were analyzed for C14 inulin or creatinine, chloride and radiosodium. The latter was injected intravenously several hours prior to tubular puncture. Net water reabsorption across the proximal tubule was less than under nondiuretic conditions. The concentration of radiosodium and of chloride in proximal tubular fluid was found to be below that of plasma in osmotic diuresis. Much steeper gradients for these ions were found across distal tubular epithelium indicating that parts other than the proximal convolution participate in the establishment of the over-all concentration gradients. Since net sodium movement occurred against an electrochemical potential gradient during osmotic diuresis, this study provides evidence for active transport of sodium ions across the proximal tubular wall.
Longitudinal and radial strain in pulse wave transmission
Authors: Van Citters Robert L. , Rushmer Robert F.
Published: December 2017

Simultaneous measurements of changes in aortic length, circumference and pressure reveal that at the beginning of systole aortic lengthening precedes the increased aortic circumference and pressure. Slight differences which were observed between circumference and pressure may be accounted for by longitudinal motion and by instrumental artifacts. The concept of active rhythm contraction of the vessel walls is not regarded as necessary to explain any of the observed phase differences between aortic pressure and dimensions.
Circulatory responses to a CO2 buffer following lethal injections of endotoxin
Authors: Hinshaw Lerner B. , Vick James A. , Nelson David L. , Wittmers Lorentz E. , Swenson Orville P.
Published: December 2017

The circulatory actions of a CO2 buffer (THAM) have been studied in the isolated perfused dog leg and kidney and in the intact dog. Techniques involving controlled arterial inflow were used in order that changes in vascular resistance could be calculated. Changes in organ weight were correlated with alterations in vascular resistance and hematocrit. Cardiac inflow was controlled and monitored in total body perfusion experiments in order that total peripheral resistance calculations and changes in venous return could be readily obtained. The infusion of THAM results in marked decreases in vascular resistance of leg, kidney and the totally perfused intact animal. Following the onset of THAM infusion there is a significant increase in venous return, brought about primarily by the reabsorption of tissue fluid. The vascular effect of THAM on the kidney may account for the profound diuretic action, although its use during prolonged hypotension appears to be detrimental. The findings of the present study indicate that the possible uses of THAM in hypertension and edema are worthy of investigation.
Effect of gallamine triethiodide and pentobarbital on certain cardiovascular and respiratory events
Authors: Greenfield Wilbert , Imig Charles J. , Evonuk Eugene
Published: December 2017

In dogs peripheral blood flow and blood pressure were not significantly altered during a period of 2 hours following the administration of Flaxedil. Heart rate increased significantly. Rectal temperature, hematocrit, O2 consumption and CO2 production were not altered. The changes in peripheral blood flow and heart rate which occur following an anesthetic dose of pentobarbital sodium were not influenced by the administration of combinations of pentobarbital and Flaxedil. Flaxedil appears to be a desirable agent to employ for controlling the muscular activity in experiments concerned with the measure of peripheral blood flow and blood pressure since this drug per se has little or no effect on these variables and thus would permit establishment of their control values. The use of this drug alone would not be permissible in painful experimental procedures.