bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood pressure and cardiac tissue responses to prostacyclin (PGI2) in various species
Authors: Collins G. A. , MacLeod B. A. , Walker M. J. A.
Published: April 2011

The effect of prostacyclin (PGI2) on blood pressure and heart rate (in vivo) and on isolated heart tissue has been investigated in different species. Isolated cardiac tissue had limited resposes to PGI2 tested at 10−13 to 10−5 M. Cultured neonatal rat heart cells did not respond to PGI2, neither did intact rat hearts or rabbit cardiac tissue. Guinea pig and rat atria showed limited dose-dependent responses to PGI2 at concentrations greater than 10−7 M. In rat atria, 10−5 M PGI2 produced a limited elevation of tissue cAMP content. When given by intravenous injection or infusion, PGI2 produced hypotension in anaesthetized primates (three species), rat, rabbit, pig, and dog. As a vasodepressor in all species, PGI2 (on a weight basis) was more active than prostaglandins of the B or E type and, in most species tested, it was approximately five times more active than PGE2. Heart responses in intact animals were often paradoxical in that decreases in heart rate often accompanied blood pressure falls.
Effect of a specific and a nonspecific vasodilator on regional blood flows in experimental heart faiiure
Authors: MacCannell K. L. , Giraud G. D. , Lederis K. , Hamilton P. L. , Groves G.
Published: April 2011

Urotensin I, a vasoactive peptide isolated from fish urophyses, has previously been demonstrated to cause specific mesenteric dilation in the dog. This mechanism of action should limit its maximal cardiovascular actions: no additional cardiovascular effects should ensue once maximal mesenteric vasodilatation is achieved. Provided that the mesenteric vasodilatation does not result in decreased flow to other organs, the agent may, therefore, offer a theoretical advantage as an afterload reducing agent. In pentobarbital anesthetized dogs which were in heart failure as a result of chronic aortico – left atrial shunt, the effects of urotensin I on cardiovascular hemodynamics were compared with the effects of a nonspecific vasodilator, sodium nitroprusside. At equidepressor doses (approximately 15% decrease in mean arterial pressure; sodium nitroprusside, 2 μg∙kg−1∙min−1 i.v.; urotensin I, 10 mU∙kg−1∙min−1 i.v.), both agents produced comparable falls in total peripheral resistance, left ventricular end diastolic pressure, and pulmonary capillary wedge pressure. Forward cardiac output was increased by both substances, although the increases were not statistically significant. Shunt flow, estimated by echocardiography, was reduced by both. In spite of the marked similarity in hemodynamic effects in this model, the two agents affected regional blood flows differently. Sodium nitroprusside did not significantly alter regional flows measured by radioactive microspheres, although calculated splanchnic, skin, and myocardial vascular resistances were reduced. In contrast, urotensin I, as in the normal dog, greatly increased mesenteric blood flow; this redistribution of cardiac output did not, however, result in underperfusion of other vital organs. These data suggest that urotensin I may be a useful agent in the reduction of afterload in heart failure, particularly since the unique mechanism of action appears to minimize the potential for adverse effects due to excessive dosage.
Antidiuretic effect of acute morphine administration in the conscious rat
Authors: Wilson N. , Ngsee J.
Published: April 2011

Morphine was administered intravenously to normal and to Brattleboro (genetically deficient in antidiuretic hormone) rats. The injection caused a significant decrease in mean arterial pressure and urine flow in all animals, including those homozygous for diabetes insipidus. It is suggested that the antidiuretic effect of morphine may occur independently of ADH release.
Inhibition of ferrochelatase by N-methylprotoporphyrin IX is not accompanied by δ-aminolevulinic acid synthetase induction in chick embryo liver cell culture
Authors: Cole Susan P. C. , Marks Gerald S. , Montellano Paul R. Oritz de , Kunze Kent L.
Published: April 2011

N-Methylprotoporphyrin has been shown to markedly inhibit ferrochelatase activity in chick embryo liver cell culture without inducing δ-aminoievulinic acid (ALA) synthetase activity. This result supports the idea that the effects of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) on ALA synthetase activity and ferrochelatase activity are dissociated and that inhibition of ferrochelatase alone is not sufficient to cause induction of ALA synthetase. We conclude that the porphyrinogenic activity of DDC can be explained only in part by the actions of N-methylprotoporphyrin.
The role of free calcium ion in calcium release in skinned muscle fibers
Authors: Stephenson Elizabeth W.
Published: April 2011

Major questions in excitation–contraction coupling of fast skeletal muscle concern the mechanism of signal transmission between sarcolemma and sarcoplasmic reticulum (SR), the mechanism of SR Ca release, and operation of the SR active transport system during excitation. Intracellular Ca movement can be studied in skinned muscle fibers with more direct control, analysis of 45Ca flux, and simultaneous isometric force measurements. Ca release can be stimulated by bath Ca2+ itself, ionic "depolarization," Mg2+ reduction, or caffeine. The effectiveness of bath Ca2+ has suggested a possible role for Ca2+ in physiological release, but this response is difficult to analyze and evaluate. Related evidence emerged from analysis of other responses: with all agents studied, stimulation of 45Ca efflux is highly Ca2+-dependent. The presence of a Ca chelator prevents detectable stimulation by ionic "depolarization" or Mg2+ reduction and inhibits the potent caffeine stimulus; inhibition is graded with chelator concentration and caffeine concentration, and is synergistic with inhibition by increased Mg2+. The results indicate that a Ca2+-dependent pathway mediates most or all of stimulated 45Ca efflux in skinned fibers, and has properties compatible with a function in physiological Ca release.
Ca2+ coupling in vascular smooth muscle: Mg2+ and buffer effects on contractility and membrane Ca2+ movements
Authors: Altura B. M. , Altura B. T. , Carella A. , Turlapaty P. D. M. V.
Published: April 2011

An examination of the literature, over the past two decades, reveals that (1) in studies of different types of vascular smooth muscles, Mg2+ is often either left out of physiological salt solutions or reduced in concentration compared with that in blood; and (2) when excitation–contraction coupling processes have been examined in isolated vascular tissues and cells, a number of artificial (synthetic) amine and organic zwitterion buffers have often been substituted for the naturally occurring bicarbonate and phosphate anions found in the blood and in cells. The influence of extracellular magnesium ions ([Mg2+]o) on tone, contractility, reactivity, and divalent cation movements in vascular smooth muscles, and how they may relate to certain vascular disease states, is reviewed. Data are presented and reviewed which indicate that many of the most commonly used artificial buffers (e.g., Tris. HEPES, MOPS, Bicine, PIPES, imidazole) can exert adverse effects on contractility and reactivity of certain arterial and venous smooth muscles. The data reviewed herein suggest that [Mg2+]o and membrane Mg are important in the regulation of vascular tone, vascular reactivity, and in control of Ca uptake, content, and distribution in smooth muscle cells. [Formula: see text] and (or) PO42−anions may be important for normal maintenance of excitability and reactivity and in the control of Ca uptake, content, and distribution in smooth muscle cells.
Calcium and excitation–contraction coupling in vascular smooth muscles
Authors: Weiss George B.
Published: April 2011

The roles of Ca2+ in excitation–contraction coupling in vascular smooth muscle have been difficult to delineate, primarily because unambiguous association of specific Ca2+ components with morphologically defined cellular structures could not be attained. More recent use of washouts in La3+-substituted solutions at low temperature (to remove superficial Ca2+ and retain cellular Ca2+), Scatchard-coordinate plots (to identify incubation conditions appropriate for examining predominantly high or low affinity Ca2+ components), and high concentrations of Sr2+ (to remove high but not low affinity Ca2+) have facilitated qualitative and quantitative separation of different Ca2+ fractions. The release of high affinity Ca2+ elicited with norepinephrine and the increase in uptake of low affinity Ca2+ obtained with high K+ have been clearly demonstrated, and may directly measure or indirectly reflect changes in the level of intracellular free Ca2+. In other types of vascular smooth muscle (e.g., renal vessels, coronary arteries), similar Ca2+ components also appear to be present, but their relative size and functional importance for regulation of contractile responsiveness can differ.
Calcium in excitation–contraction coupling of frog skeletal muscle
Authors: Taylor S. R. , Lopez J. R. , Griffiths P. J. , Trube G. , Cecchi G.
Published: April 2011

A principal step in the process leading to muscle contraction is the intracellular release of Ca2+. We have detected and compared some physical and chemical events that reflect Ca2+ release in contracting frog skeletal muscle cells, described the effects of some agents that are believed to alter intracellular Ca2+ release during contraction, and speculated about the role of Ca2+ release in influencing some of the mechanical properties of frog muscle. The specific physical features recorded were changes in striation spacing, myofibrillar orientation, and force development. The chemical feature was the relative change in intracellular [Ca2+] recorded as light emission from cells microinjected with the Ca2+-sensitive protein aequorin. The presence or absence of a correlation among these variables has been used (i) to evaluate the action of some agents thought to change intracellular Ca2+ release in excitation–contraction (E–C) coupling, (ii) to further substantiate the effects of cell length on Ca2+ release, and (iii) to examine some details of models for E–C coupling. The results show that potentiating agents enhance and prolong intracellular Ca2+ release without changing the rate of Ca2+removal during E–C coupling. This extra Ca2+ does not produce the same effect on contractions at all lengths. Contractility is inversely related to cell length, and Ca2+-induced activation is normally less than maximum not only at short lengths but also at optimal striation spacings.
Ouabain potentiation and Ca release from sarcoplasmic reticulum in cardiac and skeletal muscle cells
Authors: Fujino S. , Fujino M.
Published: April 2011

In this article, we describe a possible mechanism of ouabain potentiation in heart based on the following findings in cardiac and skeletal muscles of various species. (1) In heart ventricle muscles of frog and guinea pig, the ouabain potentiation is produced without an effect on Ca influx. In both frog and cat heart ventricle muscles, ouabain potentiates the rapid cooling contracture with or without caffeine in a Ca-deprived medium. It follows, therefore, that the ouabain potentiation is produced by an "intracellular" mechanism. (2) In crab single muscle fibers, contractile responses such as twitch, potassium-induced contracture, caffeine-induced contracture, and water-induced contracture are remarkably potentiated if ouabain is present within the fibers by microinjection, whereas the situation is reversed if the drug is given extracellularly. (3) The ouabain potentiated the Ca release from fragmented sarcoplasmic reticulum (FSR) isolated from cat, guinea pig, and frog heart and from skeletal muscles as a result of the procedures used, such as changing the ionic environment. (4) In frog, cat, and guinea pig heart ventricle muscles, a reduction of contractility as a result of pretreatment with urea–Ringer's was completely cancelled by ouabain almost without influencing the membrane depolarization. Based on these findings and others, the deduction was made that the positive inotropic effect of cardiac glycosides on the heart is brought about by potentiation of contraction – Ca release from the intracellular store sites, namely the sarcoplasmic reticulum.
Catecholamines and triiodothyronine variations and the calorigenic response to norepinephrine in cold-adapted and exercise-trained rats
Authors: LeBlanc J. , Labrie A. , Lupien D. , Richard D.
Published: April 2011

A comparison was made of the thermogenic response to norepinephrine (NE) in cold-adapted (2 h per day at −15 °C for 5 weeks) and in exercise-trained rats (2 h swimming per day for 5 weeks). The oxygen consumption and the plasma catecholamine elevation were comparable for both conditions. Similarly plasma corticosterone determinations indicated comparable elevations in acute stress exposure and reduced responses in both exercise-trained and cold-adapted rats. The marked increase in colonic temperature which was observed in cold-adapted animals injected with NE (30 μg/100 g s.c.) was not found in exercise-trained rats. Similarly the brown adipose tissue was double in size in the cold-adapted rats but remained unchanged with exercise training. An important elevation of triiodothyronine (T3) was found in cold-exposed rats, either adapted or not. However, exercise was found to decrease plasma T3 in trained and nontrained rats. The results indicate that swimming for 2 h and exposure to cold (−15 °C) for 2 h produced comparable elevation of plasma corticosterone and catecholamine, and of oxygen consumption. However, only the cold-adapted animals develop a NE-induced thermogenesis. It is suggested that thyroid hormones are necessary as permissive factor, in stress-induced thermogenesis.
Acute effects of amrinone on regional myocardial and systemic blood flow distribution in the dog
Authors: Einzig Stanley , Rao Gundu H. R. , Pierpont Mary Ella , White James G.
Published: April 2011

The effect of bolus intravenous injections of amrinone (1–2 mg/kg) on abdominal organ, central nervous system, and myocardial blood flow distribution was examined in 15 anesthetized dogs. Blood flows were measured during control conditions and 5 and 60 min following drug administration using left atrial injection of 15-μm radionuclide-labeled spheres. Analysis of variance revealed that blood flow changes were similar in dogs receiving either drug dose (P > 0.10). Five minutes following injection, blood flow was increased (all P < 0.05) in the renal cortex (+20.4%), spleen (+40.4%), and liver (+47.1%); flow was unchanged in other abdominal organs (pancreas, gallbladder, small and large intestine, and fundic and antral gastric mucosa) and the central nervous system (cervical spinal cord, pons, medulla, dorsal thalamus, cerebellum, caudate nucleus, and cerebral cortical gray and white matter); and flow was reduced in the triceps muscle (−23.7%). At this time, left ventricular flow was increased (+25.0%) and the left ventricular subendocardial/subepicardial (Endo/Epi) flow ratio was reduced (1.09 ± 0.02 (SE) vs. 0.90 ± 0.02, P < 0.001). Sixty minutes following injection, renal and hepatic flows had returned to control values while splenic flow remained increased (+61.6%); intestinal, gastric mucosal, gallbladder, and triceps flows were reduced by values ranging from 26.7 to 38.9% and central nervous system perfusion was reduced by values ranging from 11.8 to 19.4% in all regions except the caudate nucleus. Although left ventricular flow had returned to control values, the Endo/Epi ratio (1.02 ± 0.02) remained minimally reduced at this time (P < 0.001). These results suggest that vascular responsiveness to intravenous amrinone is not uniform in different circulatory beds and that relative subendocardial under-perfusion of the left ventricular myocardium occurs following bolus intravenous amrinone injections in the dog.
Effects of chronic exercise on cardiac output and its determinants
Authors: Wolfe Larry A. , Cunningham David A.
Published: April 2011

A protocol which combines the noninvasive measurement of cardiac output [Formula: see text], systolic time intervals (STIs), and blood pressure was used to evaluate the effects of jogging on cardiac function. Studies were conducted during levels of steady-state cycle ergometer exercise which represented approximately 35, 55, and 75% of aerobic capacity. Subjects were 15 healthy men (mean age = 37.2 years) and 13 healthy controls. Predicted aerobic capacity (pred [Formula: see text]) increased 15 and 17% in the training group after 3 and 6 months of training; the control group displayed a small detraining effect. Changes in the training group versus control group included significant increases in exercise [Formula: see text], stroke volume (SV), mean systolic ejection rate (MSER), and systolic blood pressure (SBP). Changes in STIs were small and usually nonsignificant. The findings, considered in relation to echocardiographic measurements from the same subjects (L. A. Wolfe, D. A. Cunningham, P. A. Rechnitzer, and P. M. Nichol. 1979 J. Appl. Physiol. 47: 207–212.), suggested that changes in cardiac output were due to an increased preload, rather than a change in exercise heart rate, reduced afterload, enhanced contractile state, or myocardial enlargement.
Effects of the adrenergic nervous system on training-induced cardiac enlargement, and on the intrinsic rate and phenylephrine sensitivity of isolated rat atria
Authors: Harri Mikko , Kuusela Pertti
Published: April 2011

Atria isolated from rats after 6 to 7 weeks running training or swim training in water at 30 °C beat at a slower rate than did the atria from sedentary control animals. If the rats received noradrenaline injections with each running session their atrial rate was even lower, while propranolol injections did not lead to lower intrinsic atrial rate. Repeated noradrenaline or propranolol injections alone or swim training in warm water (38 °C) did not result in altered atrial rate. A plot of the intrinsic atrial rate against heart weight yielded a significant (r = −0.803) negative relationship (y = 311–0.91 x). Swim training in cold water, or chronic noradrenaline injections led to a lessened sensitivity of isolated atria to phenylephrine while chronic beta blockade tended to increase the sensitivity. The results suggest that an intense, although transient, cardiac stimulation, typical of the combined action of running training and noradrenaline injections, results in a lower intrinsic atrial rate and greater cardiac enlargement, while a more sustained type of cardiac stimulation, as produced typically by repeated injections of noradrenaline, leads to less sensitivity to phenylephrine.
The toxic effects of ouabain: A voltage-clamp study
Authors: Deslauriers Y. , Ruiz-Ceretti E. , Schanne O. F. , Payet M. D.
Published: April 2011

The electrophysiologic effects of a toxic concentration of ouabain (10−5 M) were studied in frog atrial trabeculae. The toxic concentration was determined by the appearance of a negative inotropic effect and an increase in basal tension. Current- and voltage-clamp measurements were performed. Ouabain did not alter the passive electrical properties of the preparation. Under current-clamp conditions the membrane depolarized and the action potential amplitude as well as its maximum rate of rise decreased. The current–voltage curve for the fast inward current was shifted toward more positive potentials and the maximum sodium current decreased. The maximum sodium conductance was also reduced. The process of reactivation of the fast inward current was accelerated. The slow inward current and the maximum slow conductance also decreased under ouabain. These effects could explain the negative inotropic action of high concentrations of glycosides, as well as the action potential changes observed by several investigators. They also help to understand the arrhythmogenic effects of high concentrations of digitalis.
The effects of indomethacin on uterine activity and prostaglandin (PG) concentrations during labor induced by administering ACTH to fetal sheep
Authors: Evans C. A. , Kennedy T. G. , Patrick J. E. , Challis J. R. G.
Published: April 2011

To assess the importance of endogenous prostaglandins in parturition, we have examined the effects of indomethacin on maternal steroid concentrations and on the frequency and maximum amplitude of uterine contractions during delivery induced by administering adrenocorticotrophic hormone (ACTH) to fetal sheep. Uterine contractions were evaluated by measuring amniotic fluid pressure in chronically catheterized sheep, 130-days pregnant treated for 70 h with continuous infusions of intrafetal ACTH1–24, and with indomethacin or vehicle into the maternal femoral vein. Maternal plasma progesterone and estrone concentrations and fetal plasma Cortisol concentrations were estimated by radioimmunoassays (RIAs). Concentrations of prostaglandin E (PGE), PGF, and 6-oxoPGF1α (the hydrolysis product of PGI2) were measured by RIAs in myometrium, endometrium, cotyledons, amnion, and chorioallantois at different locations of the uterus. Labor was initiated after 70 h intrafetal ACTH treatment as indicated by a significant fall in maternal progesterone (P4) and rises in maternal plasma estrone (E1) and fetal plasma Cortisol concentrations, and by increased frequency and maximum amplitude of uterine contractions. indomethacin treatment had no significant effect on maternal plasma P4 or E1. Prostaglandin (PG) concentrations within uterine tissues varied with different uterine areas. However, overall, indomethacin significantly decreased concentrations of all PGs in all tissues examined, except for PGE in myometrium and endometrium. Indomethacin administration reduced the degree of cervical softening. After ACTH infusion alone there was an increase in the frequency and maximum amplitude of uterine contractions. In animals receiving concomitant indomethacin the frequency, but not the maximum amplitude of contractions, was significantly decreased. These results suggest that PGs play a role in the regulation of myometrial activity during ovine parturition, and that their action may be directed towards the modulation of the frequency of uterine contractions.
Calcium pools for noradrenaline and potassium-induced contractions of rat portal vein
Authors: Ebeigbe A. B.
Published: April 2011

The contractile responses of isolated normal and Ca-depleted rat portal veins to varying concentrations of noradrenaline (NA) and K+ have been studied with a view to further clarifying the sources of Ca for contraction using both agents. The comparably rapid times-to-peak of NA and K+ contractions of normal (Ca-containing) strips suggest mobilization of a common Ca pool, perhaps superficial; whereas, following Ca-depletion, NA appears to mobilize a superficial pool more readily than K+. Following K+ depolarization in Ca-free medium, NA produced a contraction sensitive to ryanodine, suggesting Ca release from an intracellular pool.
Development of the pancreas during gestation and lactation in swine
Authors: Charbonneau Pascale , Pelletier Ghislain , Morisset Jean
Published: April 2011

This study examined the development of the pancreas during gestation and lactation in swine. Forty-two mated sows and 42 unmated controls were sacrificed after 30, 70, and 110 days of gestation; 7.14, and 28 days of lactation; and 11 days after weaning. Their pancreas were excised, weighed, and fragments homogenized for evaluation of protein, amylase, chymotrypsin, RNA, and DNA contents. Data indicate that all these parameters were reduced at the end of the gestation period when compared with controls. During lactation, pancreatic weights, enzyme, protein, and RNA contents showed regular increases. DNA contents were significantly increased after weaning, an indication of pancreatic hyperplasia. A return to control values is not complete 11 days after weaning. These changes in the pancreas can be related to increased food intake during lactation and are probably mediated by the endogenous release of the gastrointestinal hormones cholecystokinin and secretin.
Lateral cerebral ventricle and preoptic-anterior hypothalamic area infusion and perfusion of β-endorphin and ACTH to unrestrained rats: core and surface temperature responses
Authors: Thornhill J. A. , Wilfong A.
Published: April 2011

Both β-endorphin and ACTH have been found in high concentrations within the hypothalami of mammals and each neuropeptide has been proposed to play a physiological role in regulating body temperature. In an attempt to determine how these peptides may alter thermoregulation, small, microgram concentrations of β-endorphin and ACTH were injected either into lateral cerebral ventricle (ICV) or directly into the preoptic-anterior hypothalamic area (POAH) or perfused into the POAH of unrestrained rats. Core (rectal) and surface (tail) temperatures were recorded before and after ICV and POAH injection of 1 μg of β-endorphin or ACTH or perfusion (10 ng/μL) of either neuropeptide. POAH perfusion of naloxone HCl following the neuropeptide perfusion was tested to determine the specificity of the temperature responses. Regardless of the route of central administration, β-endorphin, in the concentrations used, consistently evoked a hyperthermic core temperature response, that could be antagonized by naloxone. Increased core temperatures may, in part, have been due to peripheral vasoconstriction, as suggested by the decreases seen in tail temperature. The same concentrations of ACTH failed to show any prominent core temperature changes. Results suggest that β-endorphin is a more potent modulator than ACTH in altering core temperatures of unrestrained rats. Whether β-endorphin and ACTH act physiologically in an antagonistic manner to maintain a constant body temperature remains to be proven.
Radioiodination of p-hydroxyphenylisopropyladenosine: development of a new ligand for adenosine receptors
Authors: Munshi Ravi , Baer Hans P.
Published: April 2011

dl-p-Hydroxyphenylisopropyladenosine has been iodinated with 125I and tested as a ligand of adenosine receptors in membranes from rat brain using a filtration assay. Binding studies using l-[3H]phenylisopropyladenosine as a ligand were carried out in parallel, and the binding of both ligands could be displaced by dl-p-hydroxyphenylisopropyladenosine and l-phenylisopropyladenosine in a similar fashion. These data establish the feasibility of using radioiodinated derivatives of adenosine as ligands of suitable types of adenosine receptors.
The pathophysiology of superoxide: roles in inflammation and ischemia
Authors: McCord Joe M. , Roy Ranjan S.
Published: April 2011

The superoxide radical plays major roles in the neutrophil-mediated acute inflammatory response and in postischemic tissue injury, although the sources and actions of the radical are quite different in these two pathological states. While neutrophils produce superoxide for the primary purpose of aiding in the killing of ingested microbes, a second useful function has evolved. The superoxide released from actively phagocytosing neutrophils serves to attract more neutrophils by reacting with, and activating, a latent chemotactic factor present in plasma. Superoxide dismutase, by preventing the activation of this superoxide-dependent chemotactic factor, exerts potent anti-inflammatory action. During ischemia, energy-starved tissues catabolize ATP to hypoxanthine. Calcium transients in these cells appear to activate a calmodulin regulated protease which attacks the enzyme xanthine dehydrogenase, converting it to a xanthine oxidase capable of superoxide generation. When the tissue is reperfused and reoxygenated, all the necessary components are present (xanthine oxidase, hypoxanthine, and oxygen) to produce a burst of superoxide which results in extensive tissue damage. Ischemic tissues are protected by superoxide dismutase or allupurinol, an inhibitor of xanthine oxidase.
Importance of medullary events in ammonium excretion: studies in acute respiratory and acute metabolic acidosis
Authors: Gougoux Andre , Vinay Patrick , Lemieux Guy , Goldstein Marc , Stinebaugh Bobby , Halperin Mitchell
Published: April 2011

The renal medulla can play an important role in acid excretion by modulating both hydrogen ion secretion in the medullary collecting duct and the medullary [Formula: see text]. The purpose of these experiments was to characterize the intrarenal events associated with ammonium excretion in acute acidosis. Cortical events were monitored in two ways: first, the rates of glutamine extraction and ammoniagenesis were assessed by measuring arteriovenous differences and the rate of renal blood flow; second, the biochemical response of the ammoniagenesis pathway was examined by measuring glutamate and 2-oxoglutarate, key renal cortical metabolites in this pathway. There were no significant differences noted in any of these cortical parameters between acute respiratory and metabolic acidosis. Despite a comparable twofold rise in ammonium excretion in both cases, the urine pH, [Formula: see text], and the urine minus blood [Formula: see text] difference (U-B [Formula: see text]) were lower during acute hypercapnia. In these experiments, the urine [Formula: see text] was 34 mmHg (1 mmHg = 133.322 Pa) lower than that of the blood during acute respiratory acidosis while the U-B [Formula: see text] was 5 ± 3 mmHg in acute metabolic acidosis. Thus there were significant differences in medullary events during these two conditions. Although the urine pH is critical in determining ammonium excretion in certain circumstances, these results suggest that regional variations in the medullary [Formula: see text] can modify this relationship.
Canine coronary venous pressures: responses to positive inotropism and vasodilation
Authors: Klassen G. A. , Armour J. A.
Published: April 2011

The epicardial coronary venous pressure in 16 dogs was compared with coronary arterial pressure as well as aortic, intraventricular, and intramyocardial pressures. Partial aortic occlusion augmented intraventricular (IVP), intramyocardial (IMP), aortic (AP), and coronary arterial pressures. Peripheral coronary venous pressure was also elevated. Dobutamine significantly augmented IVP and IMP but not aortic or central coronary artery pressures; this agent significantly elevated coronary venous systolic pressure (28/8 to 84/12 mmHg) (1 mmHg = 133.322 Pa). Nitroglycerine decreased IVP, IMP, and AP significantly. Central coronary arterial pressure also fell significantly, but coronary venous pressures remained unchanged. In contrast dipyridamole resulted in no change in IVP, IMP, AP, or coronary arterial systolic pressures; however, the peripheral coronary venous systolic pressure became significantly elevated. Thus the two vasodilators, nitroglycerine and dipyridamole, had different effects upon coronary venous pressure. These data reinforce the recently expressed view that coronary veins behave in a complex fashion and further suggest that their pressures are dependent upon coronary artery pressure, intramyocardial pressure, and coronary venous tone.
Glucose homeostasis during the early stages of liver regeneration in fasted rats
Authors: Petenusci Sérgio O. , Freitas Thelma C. , Roselino Eduardo S. , Migliorini Renato H.
Published: April 2011

Kinetic studies with [2-3H]glucose in vivo and gluconeogenic activity measurements in vivo and in vitro were performed in 70% hepatectomized rats submitted to fasting, which represents an extra burden for glucose synthesis but does not impair liver regeneration. Rates of glucose replacement, under steady-state conditions, 14 and 24 h postoperatively, did not differ in partially hepatectomized fasted rats and sham-operated controls. Phosphoenolpyruvate carboxykinase activities increased more rapidly during fasting in remnant livers than in intact livers from controls. Rates of incorporation of 14C from alanine into circulating glucose in hepatectomized rats were already maximal 14 h after surgery, whereas in controls they continued to augment. The maximal rates after partial hepatectomy could not be surpassed by performing the operation in diabetic animals. It is concluded that the relatively high blood sugar levels during fasting in hepatectomized rats do not depend on a reduced peripheral utilization of glucose, but only on a rapid increase in the gluconeogenic activity. The data suggest that hepatocytes in remnant liver can proliferate under conditions of maximal gluconeogenic and low glycolytic activities.
Isoniazid-induced hepatic steatosis in rabbits: an explanation for susceptibility and its antagonism by pyridoxine hydrochloride
Authors: Whitehouse L. W. , Tryphonas L. , Paul C. J. , Solomonraj G. , Thomas B. H. , Wong L. T.
Published: April 2011

Steatosis was induced in rabbits by subacute administration of isoniazid (INH, 50 mg/kg po). Concomitant treatment with pyridoxine (vitamin B6, 25 mg/kg po) antagonized both development of the hepatic lesions and the elevation of plasma concentrations of lipids. Rabbit acetylating ability was sixfold that of male Wistar rats, a species susceptible to hepatic cell necrosis, whereas hepatic cytochrome P-450 and NADPH-cytochrome c reductase were significantly lower than that observed in control or phenobarbital-induced rats. Examination of the hepatic hydrolysis of the amide bonds of INH and acetylisoniazid (AcINH) indicated that the isonicotinoyl bond of AcINH was the bond most susceptible to amidase hydrolysis in both species; but rabbits possessed the greater amidase activity: 5- to 20-fold greater than control rats and 2- to 7-fold greater than the phenobarbital-induced rats. Consequently, INH-induced hepatic fatty degeneration in rabbits was attributed to increased hepatic exposure to INH-derived primary amine functional groups, and its antagonism by vitamin B6 was attributed to the deactivation of the primary amine by pyridoxal hydrazone formation.
Involvement of estrogens in the regulation of granulosa cell aromatase activity
Authors: Daniel S. A. J. , Armstrong D. T.
Published: April 2011

Androgens have been shown to enhance follicle-stimulating hormone (FSH) induced aromatase activity in cultured granulosa cells obtained from the ovaries of immature rats, however, aromatizable androgens are more effective than nonaromatizable androgens. The present study was designed to investigate the possibility that aromatization of androgens to estrogens is responsible for the greater effectiveness of aromatizable androgens. Granulosa cells were cultured during a 36-h induction period in the presence of FSH, FSH + testosterone, or FSH + dihydrotestosterone with or without 4-acetoxy-4-androstene-3,17-dione (4-acetoxy-A), an inhibitor of aromatase activity. Treatment with androgens enhanced aromatase activity measured as accumulation of estradiol-17β during a 6-h test period with testosterone added as substrate. The effects of both androgens on FSH-induced aromatase activity were blocked by 4-acetoxy-A. Presence of a high concentration of diethylstilbestrol (DES), a synthetic estrogen, during the induction period had a significant positive effect on FSH-induced estradiol-17β accumulation during the test period. All lower doses were ineffective. Nafoxidine, an antiestrogen known to inhibit binding of estrogens to their intracellular receptors, had no effect on enhancement of FSH-induced aromatase by testosterone. The results of these experiments suggest that estrogens synthesized by granulosa cells in culture are only partially responsible for the greater ability of testosterone to enhance FSH-induced aromatase activity compared with that of dihydrotestosterone (DHT). Other factors such as differential rates of androgen metabolism and receptor affinities are probably the major determinants of androgen potency.
The action of the ionophore ionomycin in guinea-pig intestinal smooth muscle
Authors: Bolger G. T. , Triggle C. R. , Triggle D. J.
Published: April 2011

The ionophore ionomycin produced concentration-dependent (5 × 10−9 to 5 × 10−6 M) contractions in guinea-pig ileal longitudinal smooth muscle. Responses were dependent on extracellular Ca2+, consistent with the known role of this Ca2+ source in supporting excitation–contraction coupling to a variety of stimulants in this tissue. Responses were insensitive to atropine (10−6 M) but were dependent upon extracellular Na+ and were completely blocked by low concentrations of the Ca2+-channel antagonists nicardipine. YC-93 (5 × 10−7 M), and D-600 (5 × 10−6 M). The behaviour of ionomycin is very similar to that shown by A 23187 in this tissue. Ionomycin, like A 23187, can apparently activate D-600 sensitive Ca2+ channels in the guinea-pig intestinal smooth muscle rather than simply translocating Ca2+EXT.
Dissociation constants (KA) and relative efficacies of sympathomimetic amines in isolated atria during hypothermia-induced supersensitivity
Authors: Broadley Kenneth J. , McNeill John H.
Published: April 2011

Hypothermia increases the sensitivity of isolated cardiac muscle to stimulation by β-adrenoceptor agonists. The purpose of this study was to determine pharmacologically whether this supersensitivity is associated with a change in the affinity of agonists for the receptor. The positive inotropic and chronotropic responses of guinea-pig paced left and spontaneously beating right atria were recorded. Cumulative dose–response curves to noradrenaline (or adrenaline) were compared with isoproterenol in each tissue. At 38 °C, the rate curves were to the left of the tension curves, with lower mean effective concentration (EC50) values. However, this difference was less for noradrenaline and adrenaline which were therefore tension selective relative to isoproterenol. Lowering the temperature to 25 °C induced supersensitivity, all dose–response curves being displaced to the left. In the presence of carbachol the curves were shifted to the right with depression of the maxima. Dissociation constants (KA) were calculated from plots of reciprocals of equiactive concentrations obtained before and in the presence of carbachol. KA values for rate and tension responses of each agonist were identical at 38 °C, indicating that the rate selectivity was not due to affinity differences. The efficacies (er) of noradrenaline and adrenaline were greater than isoproterenol for tension, but smaller for rate responses, which may explain their relative tension selectivity. At 25 °C the KA values of all agonists were reduced approximately 10-fold. Hypothermia-induced supersensitivity is therefore associated with an increase in affinity for the cardiac β-adrenoceptor.
Evidence for an inotropic positive action of cGMP during excitation–contraction coupling in frog sartorius muscle
Authors: Mancinelli L. , Fanò G. , Ferroni L. , Secca T. , Dolcini B. M.
Published: April 2011

Within the realm of the general hypothesis concerning the role of cGMP on intracellular calcium regulation in biological systems, we have investigated the action of cyclic nucleotides during excitation–contraction coupling in frog sartorius muscle. Our data show that several guanosine nucleotides (GTP, GDP, dibutyryl-cGMP) can increase the isometric twitch tension with a maximum increase of 40% in the muscles treated with cGMP. This increase is completely independent of external Ca2+ concentration. The use of dantrolene sodium (known to inhibit calcium release from sarcoplasmic reticulum) results in a decrease in the twitch tension with a contemporary decrease in the intracellular levels of cGMP; whereas, the addition of cGMP to the muscles treated with dantrolene antagonizes, at least partially, the effect of the drug on tension development. Finally, in chemically skinned muscles, cGMP induces a reversible contracture equal to approximately one-half of that evoked by 10−4 M Ca2+.
Mode of action of ergonovine on isolated porcine coronary artery: the role of Ca2+
Authors: Rosenberger Lois B. , Griffin M. A. , Stanton H. C.
Published: April 2011

Coronary vasoconstrictor responses to ergonovine were examined in helical coronary arterial strips of young swine. Both ergonovine and serotonin (5-hydroxytryptamine) produced dose-dependent contractions of the strips. The distal region (< 1.00 mm outer diameter) of the circumflex coronary artery was most sensitive to the responses of serotonin and ergonovine. Methysergide and nifedipine significantly depressed the contractions induced by ergonovine and serotonin. Atropine, propranolol, and the alpha, blocker, prazosin, did not antagonize ergonovine-induced contractions. The ergonovine response may depend entirely upon extracellular Ca2+ while the effect of serotonin may be mediated in part through the mobilization of intracellular Ca2+ stores. Increases in 45Ca2+ cellular contents occurred after ergonovine or serotonin and these increases were blocked by methysergide or nifedipine at concentrations which blocked mechanical responses to the agonist. It is concluded that the contractions of the porcine coronary artery produced by ergonovine and serotonin are as follows: (i) regionally sensitive; (ii) blocked by Ca2+ antagonists and therefore may utilize Ca2+ channels similar to those described in other excitable tissues; (iii) blocked by methysergide. These studies indicate that the major mechanism of ergonovine's action in the porcine coronary artery is through the activation of serotonin receptors on coronary arteries which are, in turn, linked to Ca2+ channels. However, this mechanism of action may be different in an intact animal.
The gill withdrawal reflex is suppressed in sexually active Aplysia
Authors: Lukowiak Ken , Freedman Lee
Published: April 2011

In Aplysia, the central nervous system and peripheral nervous system interact and form an integrated system that mediates adaptive gill withdrawal reflex behaviours evoked by tactile stimulation of the siphon. The central nervous system (CNS) exerts suppressive and facilitatory control over the peripheral nervous system (PNS) in the mediation of these behaviours. We found that the CNS's suppressive control over the PNS was increased significantly in animals engaged in sexual activity as either a male or female. In control animals, the evoked gill withdrawal reflex met a minimal response amplitide criterion, while in sexually active animals the reflex did not meet this criterion. At the neuronal level, the increased CNS suppressive control was manifested as a decrease in excitatory input to the central gill motor neurons.
Spontaneously hypertensive rats exhibit an enhanced mydriatic response to clonidine. Evidence for enhanced sensitivity of central α2-adrenoceptors
Authors: Yarbrough G. G. , Taylor D. A. , Antolik E. K. , Robinson E. L.
Published: April 2011

Comparisons among spontaneously hypertensive (SHR), Kyoto Wistar (KW), and Wistar (W) rats were made of the functional states of central nervous system (CNS) α2-adrenoceptors (clonidine-induced mydriasis) and nonvascular peripheral presynaptic α2-adrenoceptors (clonidine-induced inhibition of the neurogenic twitch of the isolated vas deferens). While there were no differences among the strains of rats in the concentration of clonidine required to produce a 50% inhibition of the electrically evoked contractile response of the vas deferens, there was a signficant reduction in the mean effective concentration (ED50) of clonidine to induce mydriasis in SHR as compared with KW and W rats. These observations indicate that CNS α2-adrenoceptors may be functionally more sensitive in SHR. The data also suggest that the sensitivity of nonvascular presynaptic α2-adrenoceptors, at least in the vas deferens, is not altered in hypertensive animals.
Hypertension: cation transport and the physical properties of erythrocytes
Authors: Wolowyk M. W. , Slosberg B. N.
Published: April 2011

In recent years, many reports have appeared describing altered Na+ and K+ transport in erythrocytes of individuals with essential hypertension. Collectively, the interpretation of these results has been unclear. Our studies revealed that the active ouabain-sensitive K+ influx, the furosemide-sensitive K+ influx and the residual passive K+ influx in both human and rat erythrocytes can vary considerably among individual persons or rats and that these measurements alone can not be used to distinguish normotensive from hypertensive individuals. The only consistent cation transport difference observed was an increased Na+ permeability in spontaneously hypertensive rat (SHR) erythrocytes. We have also examined certain physical properties (equilibrium density distribution and sedimentation velocity) of erythrocytes from normotensive Wistar–Kyoto (WKY) and SHR rats, since these characteristics may be altered in response to abnormalities of ion transport. It was found that the erythrocytes from geographically, environmentally, and age-matched littermates of WKY and SHR rats have identical equilibrium density distributions. It was also found that the density distribution of erythrocytes can vary among geographically dispersed colonies of the same strain of rat, and even among successive litters of the same rat colony. However, the sedimentation time required for erythrocytes to reach their equilibrium density was always shorter in the normotensive WKY samples than in the matched SHR. Utilizing a simple centrifugation method, we were able to clearly show that for any population of erythrocytes with the same upper limit of cell density, normotensive WKY cells always sediment at a faster rate than those of the hypertensive SHR. In light of these results, further studies considering erythrocyte density: sedimentation velocity in humans with and without essential hypertension are indicated.
Cholinergic control mechanisms for immunoreactive motilin release and motility in the canine duodenum
Authors: Fox J. E. T. , Daniel E. E. , Jury J. , Track N. S. , Chiu S.
Published: April 2011

The relationship of immunoreactive (IR) motilin release from the duodenum to duodenal motility changes was investigated in anaesthetized dogs. Stimulation of one or both vagi at 5 or 15 Hz or field stimulation of intrinsic duodenal nerves produced Significant increases in duodenal vein IR motilin concentrations and accompanying increases in duodenal motility. However, only stimulation of both vagi at 15 Hz produced significant changes in peripheral venous concentrations of IR motilin. These occurred after a delay at a time when both the duodenum and the antrum were quiescent. Either hexamelhonium or atropine blocked IR motilin release induced by stimulation of intrinsic or extrinsic nerves while only atropine inhibited the release induced by intraarterial carbachol. The response stimulated by carbachol and blocked by atropine was tetroclotoxin insensitive and the muscarinic receptor involved was presumably located on a nonneural structure. The site sensitive to hexamethonium was presumably the neural pathway which terminated at the muscarinic receptor. Concomitant studies of duodenal motility responses to vagal and field stimulation suggested a conventional neural pathway with preganglionic cholinergic nerves in the vagus, postganglionic cholinergic nerves in the duodenum (activated by field stimulation) and a smooth muscle muscarinic receptor. Activation of antral motility by stimulation of the abdominal vagus or intraarterial carbachol injections to the antrum increased duodenal IR motilin release in the absence of duodenal motility. Thus activation of the intrinsic nerves which cross the pylorus initiated IR motilin release as well as inhibited duodenal motility. Aside from this motility-independent release there was a close correlation between increased duodenal motility and IR motilin release. These findings imply that the rise in endogenous IR motilin levels associated with the passage of the activity front of the migrating motor complex through the duodenum may be initiated by the combined effects of increased vagal activity and increased gastric and duodenal motor activity.