bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversal of high-fat diet-induced obesity in female rats
Authors: Bartness T. J. , Polk D. R. , McGriff W. R. , Youngstrom T. G. , DiGirolamo M.
Published: December 2017

The purpose of the present study was to test whether the degree of obesity or the duration of the obese state affects the reversibility of diet-induced obesity. This was accomplished by initially feeding adult female Wistar rats either a low-fat diet (Chow) or one of two high-fat diets (HFDs; 30 and 60% of total calories as dietary fat; 30% HFD and 60% HFD, respectively). Fifty-four days, reversal 1 (R1), or ninety-seven days, reversal 2 (R2), later the HFDs were substituted with the low-fat control diet in subgroups of rats. Animals from all groups were sampled at three intervals: the start of R1 (R1 start), and the completion of R1 (R1 end) and R2 (R2 end). At the end of each interval the 60% HFD-fed group had increased body weight, carcass lipid content, and retroperitoneal and parametrial white adipose tissue (RWAT and PWAT) pad weight, fat cell diameter, and fat cell volume, but not fat cell number (FCN), compared with the other groups. The 60% HFD-fed rats also exhibited a marked and persistent hyperphagia that continued even as most of the indexes of obesity approached their maximal values (R1 end). The 60% HFD group had a transient increase in RWAT and PWAT lipoprotein lipase activity that followed the development of most obesity indicators. A clear intermediate level of obesity did not develop in the 30% HFD-fed group. Instead, these animals had nonsignificant increases in these measures of adiposity, making it impossible to test whether the severity of the obesity affected its reversibility in age-matched groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Does reducing the rate or efficiency of digestion reduce food intake?
Authors: Ramirez I.
Published: December 2017

Two strains of rats (Charles River CD and Lewis) were fed high-moisture (71% water) diets containing 50-300 mg acarbose/kg dry diet for 1-3 wk. Acarbose impaired carbohydrate digestion in both strains, as evidenced by increased fecal excretion and increased intestinal contents. For both strains the highest dose of acarbose tended to stimulate food intake, whereas an intermediate dose (100 mg/kg) inhibited food intake. The lowest dose (50 mg/kg) had no significant effect. In general the food intake-promoting effect of acarbose was more pronounced in CD rats, whereas the food intake-inhibiting effect of acarbose was more pronounced in Lewis rats. To determine whether increased intestinal bulk, due to undigested food, was responsible for the reduced food intake, another experiment was conducted in which Lewis rats were fed diets containing 5-25% cellulose. Although this level of cellulose should have increased fecal bulk to the same degree as acarbose, cellulose increased rather than decreased food intake. It is proposed that the presence of incompletely digested food in the digestive tract can inhibit food intake for several days. Because manipulating diet moisture altered energy intake without altering percentage of food excreted as feces, it is proposed that acarbose and diet moisture alter food intake by different mechanisms.
Developmental changes in hindlimb muscles and diaphragm of sheep
Authors: Finkelstein D. I. , Andrianakis P. , Luff A. R. , Walker D. W.
Published: December 2017

In this study, plasma thyroxine, contractile and histochemical (adenosinetriphosphatase and NADH) characteristics of soleus (SOL), medial gastrocnemius (MG), and extensor digitorum longus (EDL) were examined in 140-day-gestation fetal sheep and in 2-, 5-, and 30-day-old lambs and adult ewes. Electrophoretic separation of myosin heavy chains was also done on all muscles and the diaphragm. There were no differences in the twitch contraction and relaxation times of MG and EDL at the different ages; in contrast SOL contraction times were significantly shorter in the fetus and newborn than in the adult. Fast glycolytic fibers first appeared in EDL, MG, and diaphragm at 5, 30, and 5 days after birth, respectively. The proportion of slow oxidative fibers decreased after birth and with postnatal development in EDL, whereas they increased in MG and diaphragm. Plasma thyroxine concentrations were higher in the fetus and day-old lambs than in 2-, 5-, and 30-day-old lambs or adult sheep. It is suggested that contractile specialization of the fast-twitch diaphragm, MG, and EDL is largely achieved in utero and is probably mediated by thyroid hormone. In contrast, SOL changed postnatally, probably influenced by the altered neural drive.
Indomethacin attenuates exercise-induced proteinuria in hypertensive miniature swine
Authors: O'Hagan K. P. , Hora D. F. , Zambraski E. J.
Published: December 2017

Exercise-induced proteinuria may be increased in hypertensives. The mechanisms underlying the increased proteinuria are not known, and it has not been determined whether animal models of hypertension exhibit a similar response. We investigated whether indomethacin (Indo) altered exercise-induced proteinuria in normal and hypertensive deoxycorticosterone acetate (DOCA) Yucatan miniature swine (YMS). Five normal and four DOCA YMS underwent 30 min of treadmill exercise at 80% of maximal heart rate. Cumulative (exercise + recovery) albumin excretion in the DOCA YMS was 25-fold (P < 0.01) greater than observed in the normal YMS. Indo had no effect on resting or exercise-induced proteinuria in the normal YMS. However, Indo decreased the slightly elevated proteinuria at rest, and normalized the exaggerated exercise-induced proteinuria in the DOCA YMS. The antiproteinuric effect of Indo in the DOCA YMS was not associated with altered exercise, recovery blood pressure, or glomerular filtration rate. Thus hypertensive DOCA YMS exhibit an exaggerated exercise-induced proteinuria. It is suggested that eicosanoids are involved in this abnormal renal proteinuric response to exercise.
Pulmonary vascular response to anaphylaxis in isolated canine lungs
Authors: Shibamoto T. , Hayashi T. , Sawano F. , Saeki Y. , Matsuda Y. , Kawamoto M. , Koyama S.
Published: December 2017

We determined changes in vascular resistance and microvascular permeability during anaphylactic reaction in isolated canine lungs perfused at constant pressure with autologous blood. In lungs with anaphylaxis induced by an intra-arterial injection of Ascaris suum antigen (10 mg), pulmonary vascular resistance and capillary pressure assessed as double occlusion pressure increased transiently by 10 times and 6.3 mmHg, respectively. Pre- to postcapillary vascular resistance ratio decreased from 0.89 +/- 0.05 to 0.21 +/- 0.06, suggesting predominant pulmonary venoconstriction. In lungs perfused in the antidromic direction from the pulmonary vein to the artery, anaphylaxis caused marked precapillary vasoconstriction, consistent with pulmonary venoconstriction. Vascular permeability assessed using the capillary filtration coefficient and isogravimetric capillary pressure did not change significantly for 3 h in either group. No changes were found in any variables in the saline-injected control lungs. The final weight of the anaphylactic lungs was significantly greater than that of the control lungs. Thus we conclude that anaphylaxis in isolated canine lung produces an increase in capillary pressure due to pulmonary venoconstriction without significant changes in vascular permeability. Pulmonary edema accompanied by anaphylactic hypotension may result from an increase in pulmonary hydrostatic intravascular pressure but not an increase in pulmonary vascular permeability.
Influenza virus-induced changes in rabbit sleep and acute phase responses
Authors: Kimura-Takeuchi M. , Majde J. A. , Toth L. A. , Krueger J. M.
Published: December 2017

Systematic investigations of sleep after viral inoculation have not previously been described. In the present study, rabbits were inoculated intravenously (iv) with control allantoic fluid followed by two sequential inoculations of influenza virus at intervals of 24 h. After each i.v. inoculation, sleep and brain temperature (Tbr), as well as leukocyte distributions and serum levels of antiviral activity and ceruloplasmin, were monitored. The first viral inoculation elicited several acute phase responses, including increased non-rapid-eye-movement sleep (NREMS), Tbr, serum antiviral activity, and serum ceruloplasmin levels, as well as neutrophilia and lymphopenia. In contrast to the effects of the first inoculation, after the second inoculation of virus, all these acute phase parameters were diminished or absent (the hyporesponsive state). Inoculation of naive rabbits with heat-inactivated virus was similarly ineffective; however, inoculation of this group of rabbits with viable virus 24 h later did induce full-scale acute phase responses. The possible role of cytokines in mediating the acute phase response after influenza viral challenge is discussed. Results support the hypothesis that sleep is a facet of the acute phase response involved in host defense mechanisms.
Effect of kinin receptor antagonists on renal hemodynamic and natriuretic responses to volume expansion
Authors: Fenoy F. J. , Roman R. J.
Published: December 2017

The role of kinins in the natriuretic and papillary blood flow (PBF) responses to intravenous administration of 0.9% sodium chloride solution equal to 5% of body weight over 30 min was evaluated using a B1-kinin receptor antagonist (des-Arg9, [Leu8]bradykinin, 2.5 micrograms/min i.v.) and a B2-kinin receptor antagonist (D-Arg, [Hyp3,Thi5,8,D-Phe7]bradykinin, 2.5 micrograms/min i.v.). In control rats, PBF increased 43 +/- 5% after the volume expansion with saline. Administration of the B1-kinin receptor antagonist had no significant effect on basal PBF or the rise in PBF produced by volume expansion. In contrast, administration of the B2-kinin receptor antagonist decreased basal PBF by 18 +/- 3% and prevented the rise in PBF during volume expansion. Urine osmolality was lower in the rats treated with the B1-antagonist and higher in rats infused with the B2-kinin antagonist than in control animals after volume expansion (587 +/- 47 and 1,082 +/- 83 vs. 907 +/- 124 mosmol/kgH2O, respectively). The initial natriuretic response during the first 30 min after volume expansion was similar in rats given vehicle or the kinin antagonists. However, cumulative sodium excretion over the 2-h course of the experiment was significantly lower in the rats given the B2-receptor antagonist than in control rats (92 +/- 7 vs. 101 +/- 9% of the administered load). The B1-kinin receptor antagonist had no effect on cumulative sodium excretion; however, glomerular filtration rate was 30% lower in rats receiving the B1-antagonist than in control rats after volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)
Precocious cessation of intestinal macromolecular transport by synthetic trypsin inhibitor in suckling rats
Authors: Harada E. , Hashimoto Y. , Syuto B.
Published: December 2017

The effects of repeated oral administration of the synthetic trypsin inhibitor camostat on intestinal macromolecular transport and disaccharidase development were investigated in suckling rats. By daily treatment with camostat, bovine immunoglobulin (Ig) G transport in the intestine declined more rapidly in treated than in control rats. The absorption curve shifted to the left in treated rats 3 days before the controls. Morphological inspection of treated pups showed a decline in the number of epithelial cells that absorb bovine IgG and in their vesicle size from basal to upper regions of the villi. Maltase activity precociously increased with camostat treatment. Chronic subcutaneous injection of camostat did not cause any changes in IgG transport and maltase activity. The depression of IgG transport by oral treatment with camostat was not affected by the cholecystokinin (CCK) receptor antagonist L 364718 and was not inhibited by adrenalectomy. The absorptive responses of IgG and maltase activity were not affected by CCK-8 treatment. These data indicate that oral administration of camostat induces precocious maturation of the small intestine and that the effect is not mediated via endogenous CCK released by camostat.
Cholecystokinin reduces body temperature in vehicle- but not capsaicin-pretreated rats
Authors: South E. H.
Published: December 2017

Systemic administration of cholecystokinin C-terminal octapeptide (CCK-8) decreases body temperature. However, it remains unclear whether reduction of body temperature is concomitant with suppression of food intake at CCK-8 doses that approach physiological levels. We examined rectal temperature after intraperitoneal CCK-8, 4 micrograms/kg, both in the presence and absence of a preferred food. We found that rectal temperature was significantly reduced by CCK-8 in both conditions and that the reduction of temperature coincided with the time of maximal suppression of food intake by CCK-8. In rats pretreated systemically with 25 or 175 mg/kg of the sensory neurotoxin capsaicin, both suppression of food intake and reduction of body temperature were significantly attenuated or abolished. The 25 mg/kg capsaicin treatment did not alter corneal chemosensitivity or the ability of rats to maintain normothermia at elevated ambient temperature, suggesting that capsaicin damage to neural substrates mediating CCK-8-induced reduction of body temperature 1) did not generalize to cephalic or peripheral warm-sensitive structures, and 2) was limited to fine sensory fibers accessible to intraperitoneal capsaicin application.
Adrenergic vasomotor responses in nasal mucosa of hooded seals
Authors: Folkow L. P.
Published: December 2017

In seals respiratory heat and water losses are restricted through nasal heat exchange. The heat exchange efficiency is apparently controlled through adjustments in the nasal mucosal blood flow rate and/or pattern. In this study the adrenergic mechanisms involved in regulation of mucosal blood flow were investigated. The nasal mucosal vasculature of 14 newly killed hooded seal (Cystophora cristata) pups was perfused by a constant-flow peristaltic pump with 37 degrees C oxygenated modified Krebs solution via the sphenopalatine arteries. The effects of single-dose injections of various drugs on resistance to flow were monitored with a pressure transducer. Epinephrine, norepinephrine, alpha 1-adrenoceptor agonist phenylephrine, alpha 2-agonist clonidine, beta 1-agonist dobutamine, and beta 2-agonist terbutaline caused transient pressure increases that were blocked by alpha-adrenoceptor antagonists. Papaverine and vasoactive intestinal polypeptide induced vasodilatation, showing that some basal vascular tone was present. Nevertheless, the beta 1- and beta 2-agonist isoproterenol had no effect on resistance, and none of the beta-agonists attenuated the pressor responses to alpha-agonists. In conclusion, adrenergic control of nasal mucosal blood flow in seals is essentially exerted through alpha-adrenoceptor-mediated arteriolar constriction, whereas beta-adrenoceptor-mediated dilatation seems to be of little importance. It is suggested that such sympathoadrenergic vascular mechanisms contribute to control nasal heat exchange efficiency in seals.
Angiotensin II receptor activation depolarizes rat supraoptic neurons in vitro
Authors: Yang C. R. , Phillips M. I. , Renaud L. P.
Published: December 2017

Functional studies indicate that hypothalamic magnocellular neurosecretory neurons are a target for angiotensin. The present investigation used intracellular recordings to characterize the nature and type of angiotensin II receptors on rat supraoptic nucleus neurons maintained in superfused hypothalamic explants. Of 68 cells transiently exposed to either Val5- or Ile5-angiotensin II (maximum peak concentration 1-25 microM), 34 responded with a gradual membrane depolarization (1-15 mV) that peaked in 2.2 +/- 0.4 (SD) min and was accompanied by a 17.6 +/- 4.8% reduction of input resistance. Responses persisted (and were actually enhanced) in media containing tetrodotoxin (0.5-1.0 microM) and/or nominally zero calcium, indicating a direct postsynaptic action. In 19 responsive cells, the mean reversal potential for the angiotensin-induced response was -26.4 +/- 2 mV. Bath application of the nonpeptide type-1 angiotensin receptor antagonist DuP753 (5-20 microM) reversibly blocked the angiotensin-induced depolarization in all of 11 cells tested. By contrast, equimolar applications of the type-2 antagonist PD123177 were ineffective in all seven angiotensin-responsive cells tested. These observations provide novel evidence for the existence of functional type-1 receptors on rat supraoptic nucleus neurons. The reversal potential for the angiotensin-induced response suggests mediation through a nonselective cationic conductance.
Central oxytocin inhibition of angiotensin-induced salt appetite in rats
Authors: Blackburn R. E. , Demko A. D. , Hoffman G. E. , Stricker E. M. , Verbalis J. G.
Published: December 2017

In several models of salt appetite in the rat, stimulated NaCl intake can be severely blunted by treatments associated with pituitary release of oxytocin (OT). Central administration of the potent dipsogen angiotensin II (ANG II) is known to elicit a limited salt appetite as well as thirst, but it has also been reported to stimulate pituitary OT secretion. These results suggest the possibility that the expression of ANG II-induced salt appetite in rats may be inhibited by a simultaneous central release of OT in response to this stimulus. To investigate this possibility, rats were given intracerebroventricular injections of OT-receptor antagonists before administration of 5 ng ANG II intracerebroventricularly in a 1-h two-bottle (water and 0.3 M NaCl) drinking test. This pretreatment resulted in a three- to fourfold potentiation of ANG II-induced saline ingestion, which was most prominent during the first 15 min of the test. OT-receptor antagonism did not, however, interfere with the dipsogenic properties of ANG II, nor did it stimulate saline ingestion alone in the absence of ANG II. Immunocytochemical studies demonstrated that central administration of ANG II at this dose caused pronounced c-fos expression in hypothalamic magnocellular OT and vasopressin neurons and also in OT neurons in parvocellular subdivisions of the paraventricular nucleus. These results therefore demonstrate that central administration of small doses of ANG II activates both magnocellular and parvocellular OT neurons in rats and indicate that some of the activated central OT pathway(s) may mediate an inhibitory effect that limits the salt ingestion induced by this treatment.
Prolactin and testosterone inhibit torpor in Siberian hamsters
Authors: Ruby N. F. , Nelson R. J. , Licht P. , Zucker I.
Published: December 2017

Female Siberian hamsters maintained in a winter photoperiod (8 h light/day) ceased to undergo daily torpor during infusion of prolactin (PRL) from osmotic minipumps; winter torpor was reinstated within 3 days of discontinuation of treatment. By contrast, PRL infusion was ineffective in suppressing daily torpor elicited by restricting food intake in female hamsters housed in a summer photoperiod (16 h light/day). Summer daily torpor was, however, completely inhibited in long-day gonadectomized male hamsters treated with testosterone (T). We suggest that the hyperprolactinemia, which in previous studies is characteristic of hamsters that sustain ablation of the suprachiasmatic nucleus, is incompatible with winter torpor. Summer torpor may be controlled by a mechanism less responsive to variations in plasma PRL concentration. Both winter and summer torpor are inhibited by exogenous T; it remains uncertain, however, whether sustained decreases in endogenous T secretion are as essential for the expression of summer as they are for winter torpor.
Neuromuscular control of the glottis in a primitive air-breathing fish, Amia calva
Authors: Davies P. J. , Hedrick M. S. , Jones D. R.
Published: December 2017

The neuromuscular control of the glottis, a muscular sphincter that controls air flow to and from the swim bladder, was investigated using in vitro preparations from bowfin (Amia calva). Stimulation of the ramus intestinalis branch of the vagus nerve caused an increase in isometric tension of the glottal musculature, indicating active closure. The glottis could be actively opened only by direct stimulation of muscle bundles lying lateral to the glottis. In 19 of 24 preparations supramaximal nerve stimulation (20 Hz, 10 V) caused a two-phase increase in muscle tension. Immediately after the onset of stimulation there was a rapid increase in muscle tension. After the end of the train of stimuli, the tension decreased and then again increased briefly followed by a slow return to baseline lasting approximately 60 s. The addition of hyoscine reduced maximum tension of the response by 63 +/- 7% and abolished the second slower element of the response to vagal stimulation. The remaining faster response to nerve stimulation was abolished by tubocurarine. Applied acetylcholine or carbachol mimicked the slow response, causing a slow-onset sustained contraction that was abolished by hyoscine. Hence, the musculature showed physiological characteristics of both skeletal and smooth muscle. Histological examination of the glottis confirmed the physiological results: smooth muscle fibers were found lining the pneumatic duct and lumen of the glottis arranged in a circular fashion around the lateral margins of the glottis. Distinct skeletal muscle bundles were found lateral to the smooth muscle and also arranged in parallel with the glottal lumen, forming a skeletal muscle sphincter.(ABSTRACT TRUNCATED AT 250 WORDS)
Independence of heart rate and circadian period in the golden hamster
Authors: Refinetti R. , Menaker M.
Published: December 2017

Cardiac contractions are under the influence of at least two processes of biological timing, one responsible for the mean level of heart rate (oscillations with a frequency of up to several hundred per minute) and another responsible for the circadian rhythm of heart rate (oscillations with a frequency of one per 24 h). To investigate whether the mean level of heart rate is proportional to the frequency of circadian oscillation, we compared the heart rates of normal golden hamsters (circadian period approximately 24 h) and tau-mutant hamsters (circadian period approximately 20 h). Neither in anesthetized preparations nor in freely moving animals was there a difference in heart rate between the two groups despite the 20% difference in circadian period. Thus the mean level of heart rate seems to be independent of the circadian period. It is likely that the tau gene, which affects the frequency of the circadian pacemaker, has no effect on the intrinsic frequency of the cardiac pacemaker. In vitro studies of isolated hearts or myocardial cell cultures are necessary to confirm this inference.
High NaCl intake of rat dams alters maternal behavior and elevates blood pressure of adult offspring
Authors: Contreras R. J.
Published: December 2017

The present study investigated whether differences in maternal NaCl intake altered 1) maternal-pup behavior and 2) the development of dietary obesity and blood pressure level of adult Sprague-Dawley rats maintained on a palatable high-fat/milk (HF/M) diet. Thirteen dams fed high (3%) NaCl and 12 dams fed basal (0.12%) NaCl were observed on postnatal days 2-21 for differences in the number of times spent 1) nursing, 2) in contact with or licking, sniffing, and carrying pups, and 3) in nest building. The offspring were continued on their respective NaCl diets to 30 days postpartum, and then both NaCl groups were fed an intermediate (1%) NaCl diet thereafter. Beginning at 60 days of age, the offspring from each maternal NaCl condition were fed either Agway R-M-H 1000 pelleted food or a HF/M diet for 14 wk. Dams fed 3% NaCl spent significantly more time licking their pups than did dams fed 0.12% NaCl. The adult offspring of dams fed 3% NaCl had a significantly higher level of systolic blood pressure and consumed more calories of sweetened condensed milk on the HF/M diet than did rats raised on 0.12% NaCl. Dietary-induced obesity did not magnify the increase in systolic blood pressure from high maternal NaCl intake. The present results raise the possibility that increased maternal licking may contribute to the increased blood pressure and solution intake that follows from high maternal NaCl intake.
Response of the avian kidney to acute changes in arterial perfusion pressure and portal blood supply
Authors: Glahn R. P. , Bottje W. G. , Maynard P. , Wideman R. F.
Published: December 2017

Domestic fowl kidneys autoregulate total renal blood flow and glomerular filtration rate (GFR) over a wide range of renal arterial perfusion pressure (RAPP). Sustained (approximately 2-4 h) restriction of renal portal blood flow attenuates the autoregulatory responses. The present study was designed to assess the effects of acute (approximately 10 min) alterations of renal portal blood flow on renal function, and to dissociate the renal responses to altered renal portal blood flow from the renal responses to reductions in RAPP. The thermal pulse decay (TPD) technique and p-aminohippuric acid clearance (CPAH) were used to measure blood flow. During acute increases and decreases in renal portal blood flow, regional renal blood flow as measured by the TPD system (RBFTPD) was significantly positively correlated with total kidney blood flow represented by CPAH (RBFPAH). These results indicate that changes in total kidney blood flow induced by alteration of portal perfusion were reflected in the regional measurement of renal blood flow. Changes in renal portal blood flow did not affect the urine flow rate (UFR), GFR, or fractional excretion of sodium (FENa). Reducing RAPP from 120 to 50 mmHg significantly reduced UFR, GFR, and FENa. Overall, these results indicate that large acute changes in renal portal blood flow can significantly alter total renal blood flow without significantly affecting parameters (UFR, GFR, and FENa) primarily influenced by the renal arterial vasculature.
Temperature sensitivity of neurons in slices of the rat PO/AH area: effect of bombesin and substance P
Authors: Schmid H. A. , Jansky L. , Pierau F. K.
Published: December 2017

The effects of bombesin (Bom) and substance P (SP) were investigated in 156 temperature-sensitive and -insensitive neurons in slices of the preoptic and anterior hypothalamic area (PO/AH) of rats. Application of Bom increased the firing rate (FR) in 68% (n = 38) of the warm-sensitive and in 62% (n = 39) of the temperature-insensitive neurons. One cold-sensitive neuron was excited; a second was not affected by the peptide. No neuron decreased its activity after Bom application. SP excited 80% (n = 15) of the warm-sensitive neurons and 48% (n = 29) of the temperature-insensitive neurons. Two cold-sensitive neurons were inhibited by SP, a third one was not affected. The opposite effect on thermoregulation in vivo caused by the two peptides cannot be explained simply by their relatively similar excitatory effects on the FR of PO/AH neurons. After Bom application the temperature coefficient (TC) was significantly elevated in 7 out of 11 warm-sensitive neurons and in 19 out of 21 temperature-insensitive neurons. After SP application the TC was significantly reduced in 6 out of 7 warm-sensitive and 1 out of 12 temperature-insensitive neurons. Bom caused grouped discharges (bursts) in 7 out of 42 PO/AH neurons; SP never produced bursts in the discharge pattern. The increase of the TC of warm-sensitive and the transformation of temperature-insensitive into warm-sensitive neurons by Bom might be regarded as the neurophysiological basis for the decreased body temperature after Bom application. It is concluded that the temperature sensitivity of PO/AH neurons is not an unchangeable inherent property of certain cells but may be altered or even evoked by physiological processes like the release of neuromodulators.
Limitations of methods of osmometry: measuring the osmolality of biological fluids
Authors: Sweeney T. E. , Beuchat C. A.
Published: December 2017

Osmometry is an important tool in the investigation of biological phenomena, and commercially available instruments for freezing point and vapor pressure osmometry can determine the osmolality of solutions quickly and inexpensively. However, accurate measurements of osmolality using these techniques require that the solutions have specific characteristics, and that measurements do not exceed the limitations inherent to each method or instrument. The thermodynamic principles underlying osmometry constrain the range and accuracy of each measurement method, and these must be considered in establishing the usefulness of each technique. This paper addresses the principles and limitations of routine osmometry techniques. We begin by discussing definitions of osmolality and the thermodynamic concepts of solute-solvent systems that are central to understanding osmometry of biological (i.e., aqueous) solutions. We then explore the application of various methods of measuring osmolality, the nature of errors introduced by overextension or misapplication of osmometry techniques, and the interpretation of data in the literature acquired by various methods and protocols.
A model of pulmonary atelectasis in rats: activation of alveolar macrophage and cytokine release
Authors: Kisala J. M. , Ayala A. , Stephan R. N. , Chaudry I. H.
Published: December 2017

Although atelectasis frequently occurs after surgery and trauma, and such patients have elevated body temperatures, the mechanism of temperature elevation secondary to atelectasis is unknown. Moreover, a small animal model has not been available to study the pathophysiology of pulmonary atelectasis. The purpose of this study, therefore, was to develop a model of pulmonary atelectasis in rats. Because interleukin-1 (IL-1) and tumor necrosis factor (TNF), both potent pyrogens, are produced by macrophages during infection and inflammation, our aim was also to determine whether alveolar macrophages produce IL-1 or TNF in response to atelectasis. Whole-lung atelectasis was produced in rats by ligating the left main stem bronchus while maintaining ventilation of the right lung. After a 1-h period of atelectasis, alveolar macrophages were harvested from the right and left lungs and incubated for 24 h, and the supernatants were assayed for IL-1 and TNF. Both IL-1 and TNF levels of macrophage cultures from the atelectatic lung were significantly increased compared with the control lung. These results suggest that increased IL-1 or TNF production by alveolar macrophages may be responsible for fever caused by atelectasis.
Neurogenic control of renal function in response to graded nonhypotensive hemorrhage in conscious dogs
Authors: Nelson L. D. , Osborn J. L.
Published: December 2017

The reflex control of plasma renin activity (PRA) and urinary sodium excretion (UNaV) was evaluated in 13 dogs instrumented for chronic study and maintained on a normal sodium intake (40 meq/day). Graded blood volume depletion of 14 (BVD1) and 21% (BVD2) of the estimated total blood volume was used to activate renal sympathetic nerve activity (RSNA), and experiments were conducted before and after bilateral renal denervation (DNX). In dogs with innervated kidneys, nonhypotensive BVD1 increased RSNA 40.9 +/- 10.9% (P < 0.05) above control. Blood volume depletion increased PRA from 1.95 +/- 0.52 to 3.5 +/- 0.57 ng.ml-1 x h-1 and decreased UNaV from 58.2 +/- 10.1 to 35.5 +/- 4.3 mu eq/min without changing renal blood flow or glomerular filtration rate. BVD2 failed to further activate RSNA (52.0 +/- 16.7%) but did increase PRA to 4.85 +/- 0.83 ng.ml-1 x h-1 and decreased UNaV to 17.9 +/- 2.7 mu eq/min. Renal DNX (n = 13) abolished both the PRA and antinatriuretic responses to BVD1 and BVD2. Thus volume-invoked reflex activation of RSNA, but not altered renal hemodynamics, mediates, activation of PRA and antinatriuresis. This neurogenic control of renal function may be critical to the rapid regulation of extracellular fluid volume, via alterations in urinary excretion.
Glomerular hemodynamics in aortocaval fistula rats: role of renin-angiotensin system
Authors: Nishikimi T. , Frohlich E. D.
Published: December 2017

To investigate intrarenal hemodynamics of aortocaval, arteriovenous (AV)-fistula rats and the effect of angiotensin-converting-enzyme (ACE) inhibition, micropuncture studies were obtained before and after administration of quinapril (100 micrograms.kg-1 x min-1), an ACE inhibitor. AV fistula produced by needle multipuncture was characterized by elevated left ventricular end-diastolic pressure (LVEDP), lower mean arterial pressure, and increased left and right ventricular weights. Effective renal plasma flow was lower in AV-fistula rats, and single-nephron glomerular filtration rate (SNGFR) and plasma flow (SNPF) were reduced. Single-nephron filtration faction (SNFF), stop-flow pressure, and glomerular pressure (PG) were increased. The lower SNGFR and SNPF and higher PG and SNFF were associated with higher afferent and efferent arteriolar resistances (RA and RE) and lower ultrafiltration coefficient (Kf). LVEDP correlated positively with with RA, RE, and SNFF (all P < 0.01) and negatively with SNGFR (P < 0.05) and SNPF (P < 0.01). After quinapril these variables returned toward normal. Thus this method for producing AV fistula was useful in creating mild and moderately severe cardiac failure (CHF). Intrarenal hemodynamics of AV were characterized by increased PG and SNFF and lower SNGFR and SNPF associated with increased RA and RE and lower Kf and SNPF correlated and with severity of CHF. Restoration of intrarenal hemodynamics to or toward normal with quinapril supports an important pathophysiological role of renin-angiotensin system in this CHF.
Mechanisms of acute hemoconcentration in bullfrogs in response to hypoxemia
Authors: Pinder A. W. , Smits A. W.
Published: December 2017

Three general mechanisms have been proposed to explain rapid increases in red blood cell concentration in vertebrates in response to hypoxia: spleen emptying, red blood cell swelling, and decreases in plasma volume. We have experimentally tested these potential mechanisms for the hemoconcentration of red blood cells associated with hypoxemia in cold (10 degrees C), submerged bullfrogs. The mean increase of hematocrit was approximately 1.4-fold (the increase was highly variable between individual frogs) when arterial oxygen saturation was reduced from 80% to 8% by lowering ambient O2 partial pressure (PO2). The largest response was seen when arterial oxygen saturation was below 33% (a saturation that is not unusual in submerged amphibians). There was no difference between hematocrit increases during hypoxemia in spleen-ligated compared with sham-operated frogs submerged in hyperoxic, normoxic, and hypoxic water, suggesting that spleen emptying is not the primary mechanism. Increased hematocrit was not due to red blood cell swelling: mean corpuscular hemoglobin concentration increased slightly as hematocrit increased, indicating that red blood cells shrank slightly rather than swelling. Plasma volume, measured in a separate group of animals by dilution of 51Cr-labeled autologous red blood cells, decreased almost 50% during hypoxemia, closely correlated with a mean increase of 1.76-fold of hematocrit. We thus conclude that the hematocrit increase seen during hypoxemia in bullfrogs is caused by a loss of plasma volume. This has important implications for cardiovascular function, since blood viscosity, oxygen carrying capacity, and cardiac output are all affected by changes in plasma volume.
Decreased perfusion pressure modulates renin and ANG II type 1 receptor gene expression in the rat kidney
Authors: Tufro-McReddie A. , Chevalier R. L. , Everett A. D. , Gomez R. A.
Published: December 2017

To determine whether decreased perfusion pressure affects the abundance and distribution of renin and its mRNA and the expression of the angiotensin II type 1 (AT1) receptor gene within the kidney, adult male Sprague-Dawley rats were subjected to aortic coarctation proximal to the renal arteries (Coarc, n = 8) and compared with sham-operated rats (Sham, n = 6). Renal renin distribution was determined by immunocytochemistry using a specific polyclonal antibody against rat renin. Renin mRNA was assessed by in situ hybridization to a 35S-labeled oligonucleotide complementary to rat renin mRNA. Kidney AT1 mRNA levels were determined by Northern analysis using a 1,133-base pair rat AT1 cDNA. Femoral arterial blood pressure, measured 24 h after surgery, was lower in Coarc than in Sham rats (75 +/- 5.4 vs. 122 +/- 2.3 mmHg, P < 0.05). Aortic coarctation increased the percent of juxtaglomerular apparatuses (%JGA) containing renin and its mRNA (85 +/- 2.5 and 66 +/- 2.8 vs. 49 +/- 5.3 and 36 +/- 1.7%, Coarc vs. Sham, P < 0.05) and the intensity of hybridization signals (497 +/- 89 vs. 71 +/- 12 grains/JGA, Coarc vs. Sham, P < 0.05). In addition, recruitment of renin gene expressing cells was observed along afferent arterioles in Coarc rats, whereas renin and its mRNA were limited to the JGAs in Sham rats. Renal AT1 receptor gene expression was threefold lower in Coarc than in Sham rats. We conclude that reduction of perfusion pressure after abdominal aortic coarctation acutely enhances renin gene expression and downregulates AT1 receptor gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunochemical characterization and localization of endothelin ETB receptor
Authors: Hagiwara H. , Nagasawa T. , Yamamoto T. , Lodhi K. M. , Ito T. , Takemura N. , Hirose S.
Published: December 2017

A highly specific antiserum was raised against purified bovine endothelin ETB receptor and used to determine the tissue distribution of the receptor subtype ETB and to localize the receptor immunohistochemically in the kidney, adrenal gland, lung, cerebellum, and pituitary gland whose functions are known to be under strong influence of endothelin. The antiserum raised in a rabbit specifically recognized the receptor band on Western blot analysis of membrane proteins. Furthermore, it immunoprecipitated only ETB, establishing its ETB specificity. By determination of the percentage of the total number of the endothelin receptors that is immunoprecipitable with the antiserum, the amounts of the ETB relative to those of the ET receptors were found to vary from tissue to tissue: lung (70%), cerebellum (55%), pituitary gland (50%), kidney (25%), adrenal gland (10%), and testis (< 2%). This means that, in the lung, ET is the major form, whereas in the testis, ETA is predominant, comprising >95% of the receptors. Immunohistochemical examination of tissue sections revealed endothelium localization of the ETB endothelin receptor.
Water uptake in stimulated cat skeletal muscle
Authors: Watson P. D. , Garner R. P. , Ward D. S.
Published: December 2017

Isolated vasodilated cat hindlimb skeletal muscles were perfused at constant flow and stimulated at 4 Hz for 2-4 min in three studies. Water uptake rates were measured gravimetrically or calculated from venous protein concentration changes. Venous plasma sodium, potassium, chloride, and osmolality were also measured. Maximum water uptake rates averaged 1.8 +/- 0.2 (SE) ml.min-1 x 100 g-1, reaching twice that in some experiments. Water uptake continued after stimulation had ceased. Constant-flow perfusion maintained a constant capillary pressure that was corroborated by measurements of arterial and venous perfusate pressures. Water uptake rate was not influenced by hematocrit but was highly correlated with plasma flow rate. The evidence strongly suggests that small-molecule osmotic pressure was the primary pressure causing the transcapillary water flux. Venous plasma sodium and chloride concentrations increased almost as much as protein (108 and 87% of the protein increase, respectively), as would be expected when water fluxes are driven by small-molecule osmotic pressure. Peak potassium efflux averaged 36 +/- 3 mu eq.min-1 x 100 g-1, but potassium did not contribute significantly to the osmotic gradient.
Mismatch between lipid mobilization and oxidation: glycerol kinetics in running African goats
Authors: Weber J. M. , Roberts T. J. , Taylor C. R.
Published: December 2017

Glycerol kinetics and total fatty acid (FA) oxidation of trained African pygmy goats were measured by continuous infusion of [2-3H]glycerol and indirect calorimetry during treadmill exercise at 40, 60, and 85% maximal O2 consumption (VO2max). Our main goals were 1) to determine whether rates of FA mobilization and utilization are eventually matched as exercise intensity increases, thereby minimizing reesterification to supply more FA to working muscles, and 2) to test the hypothesis that lipolytic rate is proportional to aerobic capacity by comparing low-aerobic goats with published values from highly aerobic dogs and humans. Mean rate of glycerol release in the circulation (Ra glycerol) was 3.83 +/- 0.11 at rest, 7.69 +/- 0.88 at 40% VO2max, reached a maximum of 15.32 +/- 0.95 at 60% VO2max, and returned to 10.53 +/- 0.76 mumol.kg-1 x min-1 at 85% VO2max. Lipolytic rate did not match total FA oxidation, implying that Ra glycerol cannot be used as an index of FA utilization, even during intense exercise. A large fraction of total FA released by lipolysis was reesterified at 60 and 85% VO2max, showing that FA mobilization does not limit whole animal FA oxidation at these intensities. Comparing goat, dog, and human responses reveals that mammalian lipolytic rate is scaled with aerobic capacity. High- and low-aerobic species exercising at the same %VO2max mobilize FA in exact proportion with their metabolic rate, suggesting that the relative contribution of FA to total energy provision is independent of VO2max.
On the nature of the circadian clock in mammals
Authors: Miller J. D.
Published: December 2017

The evidence for the essential role of the suprachiasmatic nucleus (SCN) for the generation and maintenance of circadian rhythms in mammals is briefly reviewed. The pharmacology of the phase-response curve is considered and a new circadian measure, the phase-dose-response surface (PDRS), is introduced. The role of neurotransmission, ion fluxes, and non-neuronal cellular elements in the generation and maintenance of circadian rhythmicity is considered. Cell culture of the SCN is proposed as a tool for the functional analysis of clock mechanism. The critical contribution of coupling and synchronization of clock elements is reviewed in the context of the explicit predictions generated by a strong coupling model of the circadian clock. Finally, the nature of the circadian output signal is analyzed from a phylogenetic viewpoint.
Angiotensin II-induced endothelium-dependent relaxation of fowl aorta
Authors: Hasegawa K. , Nishimura H. , Khosla M. C.
Published: December 2017

In the domestic fowl, angiotensin II (ANG II) decreases blood pressure in vivo and causes endothelium-dependent relaxation of aortic smooth muscles in vitro. To characterize ANG II-induced vasorelaxation, we compared endothelium-dependent vasodilatory effects of [Asp1,Val5]-ANG II (fowl ANG II) and acetylcholine (ACh) with the endothelium-independent vasorelaxing effect of sodium nitroprusside (SNP) on isometric tension of fowl aortic rings. Hemoglobin (Hb), gossypol, and N omega-nitro-L-arginine methyl ester (L-NAME), inhibitors for endothelium-derived relaxing factor (EDRF) in mammalian blood vessels, partially inhibited vasorelaxation induced by ANG II and ACh in fowl. Hb also markedly attenuated SNP-induced vasorelaxation, but not 8-bromoguanosine 3',5'-cyclic monophosphate-induced relaxation. 3,4,5-Trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8) or the removal of Ca2+ from the bathing medium attenuated the ACh-induced relaxation but did not significantly reduce vasorelaxation induced by ANG II or SNP. In the zero Ca2+ medium, aortic rings showed tachyphylaxis to ACh, while ANG II caused tachyphylaxis regardless of the presence or absence of external Ca2+. Furthermore, pretreatment of the ring with a high dose of ACh abolished the vasorelaxation response to ANG II, suggesting that ACh and ANG II may share a common Ca2+ pool. Calmidazolium, a calmodulin antagonist, abolished the vasorelaxation induced by ANG II and ACh but not that by SNP. Comparison of the vasodilatory effects of several ANG II analogues on fowl aortic rings showed an approximate potency order of [Asp1,Val5]-ANG II = [Asp1,Ile5]-ANG II > [Asn1,Ile5]-ANG II = [Sar1,Ile5]-ANG II > [Val5]-ANG III.(ABSTRACT TRUNCATED AT 250 WORDS)
ATP-MgCl2 restores gut absorptive capacity early after trauma-hemorrhagic shock
Authors: Singh G. , Chaudry K. I. , Chaudry I. H.
Published: December 2017

The aim of this study was to determine whether ATP-MgCl2 as an adjunct to resuscitation has any beneficial effect on the depressed gut absorptive capacity (GAC) after hemorrhage and, if so, whether alterations in whole blood viscosity (WBV) are, in part, responsible for those effects. Rats were anesthetized, a laparotomy was performed (i.e., trauma induced), and blood vessels were cannulated. The animals then underwent fixed pressure (40 mmHg) hemorrhage, followed by resuscitation with lactated Ringer solution. One group received 50 mumol/kg ATP-MgCl2 and another received saline during resuscitation. At 2 and 4 h after the end of hemorrhage, a 1-h D-xylose absorption test was performed. Viscosity determinations were made at corresponding time points in another set of rats subjected to sham hemorrhage, acute hemodilution, or hemorrhage and resuscitation. Results show that xylose absorption is depressed after hemorrhage and resuscitation and that ATP-MgCl2 restored it to normal. D-Xylose absorption was inhibited by glucose, indicating a facilitated transport process. Furthermore, WBV was reduced by the administration of ATP-MgCl2. Thus ATP-MgCl2 improves GAC early after hemorrhage and resuscitation, possibly by reducing WBV, and may be a useful adjunct to resuscitation, allowing for early enteral nutrition.
Expression of IGF-II/Man-6-P receptors on rat, rabbit, and human colon epithelial cells
Authors: Pillion D. J. , Grizzle W. E. , Yang M. , Meezan E. , Stockard C. R. , Ganapathy V. , Leibach F. H. , Myers R. B. , Haskell J. F.
Published: December 2017

Previous experiments from this laboratory have established the presence of receptors for insulin and insulin-like growth factor I (IGF-I) on apical membranes prepared from rabbit colon epithelial cells; however, no receptors for multiplication-stimulating activity (MSA), the rat peptide hormone equivalent of human IGF-II, were found in this tissue. In the current studies, radioligand binding assays, covalent cross-linking experiments, and immunoblot analyses using a polyclonal rabbit antiserum that recognizes the IGF-II/mannose 6-phosphate (Man-6-P) receptor, all confirmed the presence of IGF-II/Man-6-P receptors on membranes prepared from rat and human colon epithelial cells. Exposure of rat colon epithelial cell membrane fractions to 5 mM Man-6-P before incubation with 125I-labeled IGF-II increased radioligand binding. Immunoblot analysis indicated that IGF-II/Man-6-P receptors were present in both unfractionated rat colon membranes and fractions enriched with apical membranes. Rabbit and human colon epithelial cells displayed a different pattern of receptor distribution than rat colon epithelial cells, with more insulin receptors but relatively few IGF-II/Man-6-P receptors. Immunohistochemical studies using a rabbit polyclonal antiserum confirmed that IGF-II/Man-6-P receptors were present on both the apical and the basolateral surfaces of colon epithelial cells.