bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood volume restitution and growth in fetal lambs after acute hemorrhage
Authors: Kwan E. , Rurak D. W. , Taylor S. M.
Published: December 2017

The effects of 15-50% fetal hemorrhage (at approximately 1%/min) were studied in 13 pregnant ewes at 130-135 days of gestation for up to 5 days posthemorrhage. The upper limit of acute blood loss appears to be approximately 45%, and the rate of restoration of blood volume decreases with the severity of hemorrhage, particularly with hemorrhage > 30-40%. The restoration of fetal blood volume was due primarily to the restoration of plasma volume; in the animals subject to 40-45% blood loss (n = 9), red cell mass was still only 69.1 +/- 3.9% of the prehemorrhage value at day 5 posthemorrhage. There appear to be two phases in the restoration of plasma: 1) plasma volume was restored by 2 h posthemorrhage and 2) the restoration of plasma protein mass occurred primarily from 2 to 24 h. There was a significant correlation between blood volume and plasma protein mass. However, the regression line for the posthemorrhage days was shifted significantly upward in relation to that for the hemorrhage day because of a significant rise of plasma protein concentration. This may be important for the maintenance of blood volume after hemorrhage. Finally, fetal growth rate was determined by comparing fetal weight estimated in utero (from blood volume) with birth weight in 12 nonhemorrhaged control fetuses and in the 9 fetuses subject to 40-45% hemorrhage. The average rate of growth per day was 1.57 +/- 0.34% and -1.82 +/- 1.02%, respectively. The latter value is not significantly different from zero, suggesting that the acute blood loss impaired fetal growth.
Testicular regression and recrudescence without subsequent photorefractoriness in Siberian hamsters
Authors: Gorman M. R. , Zucker I.
Published: December 2017

Adult male Siberian hamsters transferred from 16 h light/day (16L) to 14 h light/day (14L) underwent gonadal regression and recrudescence over the course of 24 wk; the duration of reproductive quiescence was shorter by 10 wk than in hamsters transferred from 16L to 10L. A decrease in day length (DL) at week 12 from 14L to 10L greatly extended the duration of testicular involution, whereas transfer at week 12 from 10L to 8L was without effect. Hamsters that had manifested gonadal regression and recrudescence in 14L immediately initiated a second regression when challenged with 10L. Intermediate DLs induce gonadal regression and recrudescence without rendering hamsters refractory to shorter DLs. Intermediate DLs sufficient to initiate gonadal regression may be too long to trigger the interval timer that eventually induces refractoriness to shorter DLs and may be successively interpreted as short and long days, respectively, by Siberian hamsters.
Differential sympathetic nerve responses to nitric oxide synthase inhibition in anesthetized rats
Authors: Hirai T. , Musch T. I. , Morgan D. A. , Kregel K. C. , Claassen D. E. , Pickar J. G. , Lewis S. J. , Kenney M. J.
Published: December 2017

Recent studies have suggested that the interaction between the sympathetic nervous system and nitric oxide (NO) or nitrosyl factors may be an important means by which arterial blood pressure is regulated. We investigated whether NO synthase (NOS) inhibition modulates basal sympathetic nerve discharge (SND) in baroreceptor-innervated and -denervated, chloralose-anesthetized Sprague-Dawley rats. We recorded mean arterial pressure (MAP), renal SND, and lumbar SND before and after administration of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg iv). Two minutes after L-NAME administration in baroreceptor-innervated rats, MAP increased (+23 +/- 3 mmHg), whereas renal (-45 +/- 6%, n = 7) and lumbar (-35 +/- 2%, n = 6) SND significantly decreased from control levels. These changes persisted for up to 20 min after L-NAME administration. In baroreceptor-denervated rats, L-NAME increased MAP (+40 +/- 6 mmHg) and decreased lumbar SND (n = 7) (-37 +/- 10% from control at 20 min post-L-NAME). In contrast, renal SND progressively increased (+33 +/- 8% at 20 min post-L-NAME) from control after L-NAME administration in baroreceptor-denervated rats (n = 7). These results demonstrate that NOS inhibition can produce nonuniform changes in SND in baroreceptor-denervated rats and suggest that endogenous nitrosyl factors provide tonic excitation to lumbar SND, whereas they provide a tonic restraint to renal SND.
On the fractal nature of heart rate variability in humans: effects of vagal blockade
Authors: Yamamoto Y. , Nakamura Y. , Sato H. , Yamamoto M. , Kato K. , Hughson R. L.
Published: December 2017

The purpose of the present study was to investigate the effects of the vagal blocker atropine on the fractal nature of human heart rate variability (HRV) at rest. Approximately 10-min segments of beat-to-beat heartbeat intervals, i.e., HRV, of 10 normal subjects and 11 cardiac disease patients were measured before and after intravenous injection of 0.5-0.75 mg atropine sulfate. HRV data were analyzed by coarse graining spectral analysis (Y. Yamamoto and R. L. Hughson, Physica 68D: 250-264, 1993) to break down their total power into harmonic and nonharmonic (fractal) components. The harmonic component was used to calculate the contribution of high (> 0.15 Hz)-frequency components to total HRV power (%HF). From the fractal component, the contribution of the fractal component to total HRV power (%fractal), the spectral exponent beta, and Hurst scaling exponent (H) were calculated. For both normal subjects and cardiac patients, atropine resulted in significantly (P < 0.05) less mean HRV and significantly (P < 0.05) greater beta compared with control, whereas mean values for %fractal were as high as 70% and were not significantly (P > 0.05) different between atropine and control. The mean value of H with atropine was significantly (P < 0.05) greater than that for control. Directional changes in %HF and beta were consistent with only one exception for a patient who had the smallest change in log %HF by atropine. The normally irregular fractal pattern of resting HRV was decreased by atropine as shown by the decrease in %HF and the increase in beta.(ABSTRACT TRUNCATED AT 250 WORDS)
Castration attenuates prolactin response but potentiates ACTH response to conditioned stress in the rat
Authors: Bingaman E. W. , Van de Kar L. D. , Yracheta J. M. , Li Q. , Gray T. S.
Published: December 2017

The purpose of this study was to examine the effect of circulating androgens on neuroendocrine, autonomic, and behavioral responses to stress. The effects of conditioned stress were studied in male Sprague-Dawley rats that were intact, gonadectomized, or gonadectomized and treated with dihydrotestosterone (DHT). Intact animals received sham surgeries. Animals were stressed 3 wk after surgery. The adrenocorticotropic hormone (ACTH) response to conditioned stress was significantly potentiated (P < 0.01) in gonadectomized males compared with sham-operated and gonadectomized DHT-treated animals. In stressed rats, plasma corticosterone levels were significantly higher (P < 0.05) in gonadectomized animals compared with DHT-treated castrates. The prolactin response to stress was decreased (P < 0.01) in gonadectomized males compared with sham-operated and gonadectomized DHT-treated rats. The stress-induced increases in plasma renin activity and concentration were not altered in gonadectomized or in gonadectomized DHT-treated animals. Nonstressed DHT-treated castrates exhibited more “fearlike” behavior compared with nonstressed sham-operated and gonadectomized animals. However, conditioned stress produced the same behavioral effects in all treatment groups. The results demonstrate that the ACTH/corticosterone, prolactin, and behavioral responses to a psychological stressor are differentially regulated by circulating androgens.
Spinal angiotensin II influences reflex cardiovascular responses to muscle contraction
Authors: Stebbins C. L. , Bonigut S.
Published: December 2017

We tested the hypothesis that inhibition of angiotensin II (ANG II) AT1 receptors in the thoracic spinal cord attenuates the reflex cardiovascular response to electrically induced hindlimb static contraction (exercise pressor reflex). Consequently, in alpha-chloralose-anesthetized cats, contraction-induced increases in mean arterial blood pressure, maximal rate of rise in left ventricular pressure (dP/dt), and heart rate were compared before and after intrathecal injection of the AT1 receptor antagonist losartan (100 or 1,000 micrograms; n = 7). Losartan significantly diminished increases in blood pressure and maximal dP/dt provoked by static contraction by 33 +/- 5 and 31 +/- 6%, respectively. Conversely, these contraction-induced responses were unaffected by similar injection of ANG II into the lumbosacral spinal cord (n = 5). Moreover, intravenous injection of 100 micrograms losartan did not affect the cardiovascular response to contraction. Our data suggest that ANG II has a excitatory effect on the efferent arm of the exercise pressor reflex, which may be due to a facilitatory action on sympathetic nerve activity.
Body temperature modification of osmotically induced vasopressin secretion and thirst in humans
Authors: Takamata A. , Mack G. W. , Stachenfeld N. S. , Nadel E. R.
Published: December 2017

We examined the effect of increased body core temperature (Tes) on the plasma arginine vasopressin concentration ([AVP]p) and thirst responses to increased plasma osmolality (Posm) induced by 3% NaCl infusion for 120 min in seven healthy humans. Tes was increased by immersion of the lower legs in 41 degrees C water in a 28 degrees C room (passive heating; HT). Immersion of the lower legs in 34.5 degrees C water on a separate day served as the control (thermoneutral; NT). The 120-min hypertonic saline infusion was initiated 30 min after the onset of leg immersion and was followed by a 30-min rehydration period. Tes in HT increased by 0.21 +/- 0.04 degree C before infusion and by 0.86 +/- 0.08 degree C at the end of infusion. The change in Tes in NT before and after the infusion was negligible. Posm was increased by 15.0 +/- 1.0 mosmol/kgH2O by infusion in both NT and HT. [AVP]p increased by 3.48 +/- 0.72 pg/ml in NT and by 7.59 +/- 1.02 pg/ml in HT. Thus the increase in [AVP]p at a given increase in Posm was markedly higher in HT than in NT. The plasma renin activity response to hypertonic saline infusion in both conditions was similar. Subjective thirst rating and cumulative water intake during rehydration were higher in HT than in NT.(ABSTRACT TRUNCATED AT 250 WORDS)
Dopamine D1 or D2 antagonists enhance inhibition of consummatory ingestive behavior by CCK-8
Authors: Bednar I. , Carrer H. , Qureshi G. A. , Sodersten P.
Published: December 2017

A dopamine D1 (SKF-38393, 1 mg)- or D2 (LY-171555, 0.1 mg)-receptor agonist inhibited intake of an intraorally infused solution of sucrose by male rats, a test of consummatory ingestive behavior. Treatment with a D1 (SCH-39166, 0.1 mg) or D2 (raclopride, 0.6 mg) antagonist reversed inhibition by the respective agonist but enhanced the inhibitory effect of cholecystokinin octapeptide (CCK-8; 1.8 micrograms). It was not possible to demonstrate specific effects of D1 and D2 agonists on intake of pellets, a test that does not discriminate consummatory ingestive behavior from appetitive ingestive behavior, i.e., behavior used to obtain food. The results demonstrate specific involvement of dopamine D1 and D2 receptors in inhibition of consummatory ingestive behavior.
Effects of pulmonary denervation on renal sympathetic and heart rate responses to hypoxia
Authors: O'Hagan K. P. , Bell L. B. , Clifford P. S.
Published: December 2017

We hypothesized that the renal sympathetic nerve activity (RSNA) response to hypoxia is attenuated because of stimulation of pulmonary receptors by the increase in ventilation. RSNA was measured during 20 min of severe hypoxia (8% O2) in conscious New Zealand White rabbits with intact lung innervation and in rabbits with surgical denervation of the lungs (LDX). LDX decreased resting breathing frequency but had no effect on resting mean arterial pressure (MAP), heart rate (HR), or RSNA. In intact rabbits, 4 min of hypoxia resulted in elevated RSNA (from 14 +/- 2 to 29 +/- 3% of smoke-elicited maximum), bradycardia (delta-65 +/- 12 beats/min), and no change in MAP (delta 2 +/- 2 mmHg). Bradycardia diminished with time, but elevated RSNA was maintained throughout the 20-min exposure. LDX enhanced the initial bradycardia (delta-113 +/- 11 beats/min, P < 0.01) but had no effect on the RSNA response (35 +/- 2% of maximum) to hypoxia. LDX did not alter steady-state responses of HR or RSNA, but MAP declined over time (-11 +/- 2 mmHg). These results suggest that in conscious rabbits pulmonary receptors have a minor influence on control of sympathetic activity to viscera during severe hypoxemia.
Enhanced gustatory neural responses to sugars in the diabetic db/db mouse
Authors: Ninomiya Y. , Sako N. , Imai Y.
Published: December 2017

Sweet taste sensitivity in a genetic model of diabetes, the db/db mouse, in which a single major gene defect leads to the expression of diabetes and obesity, was studied by examining chorda tympani nerve responses to various taste stimuli, including sugars. The chorda tympani responses to four sugars, sucrose, fructose, glucose, and maltose, in adult db/db mice showed greater relative magnitudes and lower thresholds than those in adult lean mice, but responses to other basic taste stimuli, such as NaCl, HCl, and quinine HCl, were not different in the two groups. Behavioral experiments using a two-bottle preference test demonstrated that taste preference scores for the four sugars at suprathreshold concentrations, except 1.0 M, were higher in db/db than in control mice. Infant mice of 7-9 days of age possessing the genotype db/db also exhibited greater neural responses and lower thresholds for sugars than infant control mice, whereas streptozotocin-induced adult diabetic mice possessing the genotype +/+ did not exhibit larger sugar responses. These findings suggest that the enhanced sugar sensitivities observed in db/db mice are probably determined by a single major gene, db. The db gene may act on a common factor(s) involved in the stimulus-secretion coupling in the pancreatic B cell and the taste cell of db/db mice.
Central vascular flow patterns in the alligator Alligator mississipiensis
Authors: Malvin G. M. , Hicks J. W. , Greene E. R.
Published: December 2017

Many different flow patterns have been described through the central circulation of crocodilian reptiles. We tested the hypothesis that the vagus nerve stimulation promotes right-to-left (R-L) shunting in the alligator. Flow patterns were investigated before and during stimulation of the intact left vagus nerve using three methods. 1) Atrial and aortic PO2 were measured simultaneously and continuously by gas probes. 2) Atrial outflows were tracked with a blood tracer (helium). 3) Flows were assessed with echocardiography. Four different flow patterns were observed before vagal stimulation: left ventricular (LV) blood flowed into both the right (RAo) and left (LAo) aortas, whereas right ventricular (RV) blood flowed only into the LAo; both aortas received a mixture of LV and RV blood; only LV blood perfused both aortas; and RV blood flowed into both aortas, but LV blood flowed only into the RAo. During vagal stimulation, both aortas received a mixture of LV and RV blood in half of the animals, and in the other half, both aortas received RV blood, but LV blood flowed only into the RAo. Doppler and contrast echocardiography demonstrated swirling flow in the foramen of Panizza and the base of the LAo during systole. These data indicate that vagal stimulation either maintains or produces R-L shunting, flow patterns are variable, and blood can swirl in the foramen of Panizza and LAo base.
Relationships between muscle membrane lipids, fiber type, and enzyme activities in sedentary and exercised rats
Authors: Kriketos A. D. , Pan D. A. , Sutton J. R. , Hoh J. F. , Baur L. A. , Cooney G. J. , Jenkins A. B. , Storlien L. H.
Published: December 2017

Insulin resistance in skeletal muscle is associated with 1) relative increases in the proportion of glycolytic and fast-twitch muscle fibers and decreases in the proportion of more oxidative fibers and 2) a higher proportion of the saturated fatty acids in membrane structural lipids. Exercise is known to improve insulin action. The aims of the current studies were 1) to investigate the relationship between muscle fiber type and membrane fatty acid composition and 2) to determine how voluntary exercise might influence both variables. In sedentary Wistar rats in experiment 1, increased amounts of unsaturated fatty acids were found in the more oxidative insulin-sensitive red quadriceps and soleus muscles, whereas reduced levels of polyunsaturated fatty acids were found in primarily glycolytic white quadriceps muscles. In experiment 2, voluntary running-wheel exercise by adult female rats over 45 days resulted in reduced proportions of type IIb fibers (P = 0.01) and increased proportions of type IIa/IIx fibers (P = 0.03) in extensor digitorum longus muscle. The magnitude of these changes was related to the distance run (r = -0.73, P = 0.04; r = 0.79, P = 0.02, respectively). Exercise significantly increased oxidative capacity, as assessed by the proportion of intensely NADH-stained fibers (P = 0.0004) and citrate synthase (P = 0.003) and hexokinase (P = 0.04) activities. Citrate synthase activity was also increased by exercise in soleus muscle, where, as expected, no fiber type changes were detected. No significant differences in the fatty acid profile of soleus and extensor digitorum longus were found between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Dietary salt decreases cytosolic calcium in platelets from Dahl salt-sensitive rats
Authors: Ishida T. , Ishida M. , Matsuura H. , Ozono R. , Kajiyama G. , Oshima T.
Published: December 2017

To determine whether abnormal cellular Ca2+ handling is involved in salt-induced hypertension of Dahl salt-sensitive rats (DS), we investigated Ca2+ handling in fura 2-loaded platelets of DS and Dahl salt-resistant rats (DR) fed a high-NaCl (8%) or a low-NacL (0.3%) diet for 4 wk from 5 wk of age. At 5 wk of age, blood pressure, resting cytosolic Ca2+ concentration ([Ca2+]i), the thrombin-evoked increase in [Ca2+]i and the size of internal Ca2+ stores of DS were comparable with those of DR. After 4 wk on the diets, resting [Ca2+]i of DS on high-NaCl diet was lower than that of DS on low-NaCl diet, and there was no effect of high salt intake on resting [Ca2+]i in DR. In DS, high salt intake attenuated the [Ca2+]i response to thrombin in the presence of external Ca2+. In contrast, the [Ca2+]i response to thrombin in the absence of external Ca2+ was enhanced by high salt intake in DS. The size of internal Ca2+ stores was increased by high salt intake in DS but not in DR. These data suggest that it is not obligatory for hypertension to be accompanied by an increase in platelet [Ca2+]i.
Selective vagal rhizotomies: a new dorsal surgical approach used for intestinal deafferentations
Authors: Walls E. K. , Wang F. B. , Holst M. C. , Phillips R. J. , Voreis J. S. , Perkins A. R. , Pollard L. E. , Powley T. L.
Published: December 2017

We have developed a dorsal intracranial surgery that is minimally invasive and gives excellent access to either afferent or efferent vagal rootlets to produce selective deafferentations or deefferentations in the rat. We have combined this new unilateral afferent rhizotomy with a contralateral celiac branch cut (to completely deafferent the intestines) and a duodenal catheter placement 4 cm distal to the pylorus. Animals were maintained with 17 h/day access to a nutritionally complete liquid diet. Measures of first meal size, daily intake, and body weight before and after both surgeries indicated that animals with unilateral vagal deafferentiations recovered as fast and completely as sham-operated controls. Intraduodenal oleate (1.2 kcal) infusions reduced the size of the first meal in surgical controls (by 64%; P < 0.01) but not in the deafferented rats. A dual wheat germ agglutinin-horseradish peroxidase/Fluorogold protocol provides verification of sensory and motor lesions. The selective vagal deafferentation provided by the new surgery offers a useful model for determining gastrointestinal sites of nutrient detection and separating pre- and postabsorptive consequences of a meal.
Pancreatic polypeptide stimulates gastric acid secretion through a vagal mechanism in rats
Authors: McTigue D. M. , Rogers R. C.
Published: December 2017

The present study examined the effect of pancreatic polypeptide (PP) on gastric acid secretion. A 45-min infusion of PP was delivered into the jugular vein of urethan-anesthetized rats. Rat PP (100 pmol) significantly increased acid secretion over baseline; bilateral cervical vagotomy or peripheral atropine both eliminated this acid response. Neither intraperitoneal infusion nor close intra-arterial infusion of 100 pmol PP into the gastric circulation altered acid secretion. These results suggest that although PP requires intact vagal reflexes to stimulate acid output, it does not act on afferent or presynaptic efferent terminals of the vagus or directly within the stomach. Given that vagal reflexes consist of an afferent limb, an efferent limb, and a central relay, it may be that the target of circulating PP lies within the central nervous system. Indeed, previous studies from our laboratory have shown that microinjection of PP into the dorsal vagal complex results in long-lasting vagal-dependent elevation of gastric acid secretion.
Diurnal changes and adaptation by the liver of hamsters to an atherogenic diet
Authors: Robins S. J. , Fasulo J. M. , Pritzker C. R. , Ordovas J. M. , Patton G. M.
Published: December 2017

Studies were performed in freely feeding, male (F1B) Syrian hamsters fed a high-fat diet to determine the extent and manner of adaptation of the liver to diurnal changes in eating patterns and an increase in serum lipids. Serum cholesterol and triglycerides strongly paralleled changes in food consumption and were 40-50% greater during the 12-h dark period than the 12-h light period of the diurnal cycle. Hepatic cholesterol changes closely approximated changes in serum cholesterol (r = 0.916) due principally to changes in hepatic cholesteryl esters that were on average about 10-fold greater with the high-fat diet than with a chow diet. With the high-fat diet, hepatic cholesteryl esters were, however, extremely variable and were 40% greater at the mid-dark than at the mid-light period. With high fat there was also a marked increase in the secretion of very low density lipoproteins (VLDL) from the liver that were cholesteryl ester rich and closely paralleled the diurnal changes in hepatic cholesteryl esters (r = 0.911). In contrast, although with a high-fat diet biliary cholesterol secretion was increased, the increase in cholesterol in bile exhibited no diurnal pattern and with the high-fat diet was far less in magnitude than the increase of cholesterol in VLDL. Biliary cholesterol secretion is dependent on bile acid secretion. However, with the high-fat diet, neither the bile acid pool size nor bile acid secretion was increased compared with chow-fed controls. Moreover, with high fat at mid-dark period, bile acid secretion was significantly less than controls at mid-dark period. Thus in these hamsters a high-fat diet produced a marked increase in serum cholesterol that was distinctly diurnal and was compensated for by a diurnal increase in hepatic cholesteryl ester stores and the secretion of cholesteryl esters in VLDL. In contrast, cholesterol secretion in bile did not correspond to the fluctuating changes of cholesterol in the liver and was far less in magnitude than would be necessary to reduce a greatly expanded pool of hepatic cholesterol.
Effect of proANF-(31--67) on sodium excretion in conscious monkeys
Authors: Benjamin B. A. , Peterson T. V.
Published: December 2017

The purpose of this study was to determine the effect of proANF-(31--67) on renal function in conscious, chronically instrumented monkeys (Macaca fascicularis). The experimental protocol consisted of a 30-min control period followed by 60 min of peptide infusion and a 30-min recovery period. Atrial natriuretic factor (ANF)-(99--126), proANF-(31--67), of a combination of ANF-(99--126) plus proANF-(31--67) was infused at 15 pmol.kg-1.min-1. ANF-(99--126) caused sodium excretion to increase from 12.5 +/- 3 to a peak of 37.9 +/- 10.4 mueq/min, whereas fractional sodium excretion (FENa) increased from 0.69 +/- 0.2 to 2.3 +/- 0.43%. ProANF-(31--67) increased sodium excretion from 12.7 +/- 5 to a peak of 23.3 +/- 9.0 mueq/min and FENa from 0.56 +/- 0.07 to a peak of 1.15 +/- 0.4%. When ANF-(99--126) and proANF-(31--67) were infused in combination, sodium excretion increased from 9.6 +/- 3 to a peak of 5.19 +/- 12.5 mueq/min, whereas FENa increased from 0.97 +/- 0.4 to 3.9 +/- 1.1%. Mean arterial pressure decreased by approximately 10 mmHg in all three groups. These findings indicate that intravenously administered proANF-(31--67) causes an increase in sodium excretion and that when proANF-(31--67) and ANF-(99--126) are given in combination, they act in an additive fashion to increase renal sodium excretion.
Attenuation of the midbrain-evoked defense reaction by selective stimulation of medullary raphe neurons in rats
Authors: Schenberg L. C. , Lovick T. A.
Published: December 2017

In rats anesthetized with alfaxalone/alfadolone, electrical stimulation in the dorsal periaqueductal gray matter (PAG) evoked a cardiovascular defense reaction with increases in blood pressure, heart rate, femoral conductance, and respiratory activity but a decrease in renal conductance. These responses were attenuated significantly after microinjection of 200 nl 0.1 M DL-homocysteic acid (DLH) into nucleus raphe magnus (NRM, n = 12) or nucleus raphe obscurus (NRO, n = 22). The maximum reduction in the pressor response was similar after stimulation in NRM (-36.3%) and NRO (-37.3%). The reduction of the tachycardia, however, was greater after stimulation in NRM (-78.1%) compared with NRO (-34.6%). The maximum reduction in the PAG-evoked vasodilation of the hindlimb averaged -55.7% and -55.3% after stimulation of NRM and NRO, respectively, whereas the renal vasoconstriction was reduced by -66.4% and -79.0%. The PAG-evoked increase in respiratory amplitude was attenuated only after stimulation of NRO. It is concluded that neurons in NRM and NRO may be involved in modulating the level of excitability of neurons in the midbrain defense area and/or in its efferent pathway.
Suppression of meal size by intestinal nutrients is eliminated by celiac vagal deafferentation
Authors: Walls E. K. , Phillips R. J. , Wang F. B. , Holst M. C. , Powley T. L.
Published: December 2017

The arrival of nutrients in the gastrointestinal tract suppresses intake. To specify the neural pathways and receptor locations of this feedback, we examined the effects of intraduodenal infusions of 10 nutrients plus saline on short-term food intake of rats with selective deafferentations of vagal celiac branches. Three response profiles were observed: 1) isotonic saline, 5.6% glycerol, and 3% fructose did not inhibit intake of controls or selectively deafferented animals; 2) 3% glucose, 3% maltose, 3% L-phenylalanine, 12% Isocal, and 1.4% oleic acid suppressed intake of controls, but this inhibition was eliminated by vagal celiac deafferentation; and 3) 3% casein hydrolysate and 24% Isocal suppressed intake of controls and rats with selective vagotomies, although the latter exhibited significantly less suppression. In addition, elimination of celiac afferents chronically reduced meal size (i.e., first 30-min intake) without reducing daily food intake or body weight. Furthermore, D-phenylalanine infusions produced a delayed suppression of food intake in controls (possibly from intraluminal irritation); however, this reduction was eliminated with celiac deafferentation. Overall, this experiment indicates that vagal celiac afferents are critical for preabsorptive detection of some energy-yielding molecules or properties of nutrient solutions (as well as, perhaps, intraluminal inflammation), but not others, which are still detected, although only partially.
Regulation of food intake by metabolic fuels in white-crowned sparrows
Authors: Boswell T. , Richardson R. D. , Seeley R. J. , Ramenofsky M. , Wingfield J. C. , Friedman M. I. , Woods S. C.
Published: December 2017

Migratory birds rely on increased fat storage and fatty acid utilization to meet seasonal changes of energy expenditure and as a result increase food intake and fat stores before migration. To determine whether their feeding behavior is sensitive to carbohydrate and/or fatty acid utilization, white-crowned sparrows maintained on short daylength (9L15D) were injected intraperitoneally with 2-deoxy-D-glucose (2-DG) or 2,5-anhydro-D-mannitol (2,5-AM). Low doses of 2-DG (25 or 50 mg/kg) had no effect on food intake, and higher doses (100 or 300 mg/kg) significantly suppressed feeding after 1 and 2 h. No dose of 2-DG increased meal size. Similarly, low doses of 2,5-AM (25, 50, or 100 mg/kg) had no effect on food intake, and higher doses (300 and 600 mg/kg) significantly suppressed intake. These data suggest that decreased carbohydrate metabolism does not elicit feeding in this species. Importantly, these drugs, as well as insulin and glucagon, were demonstrated to increase plasma fatty acids as well as to decrease feeding. Injections of tributyrin (100, 300, 600, or 2,000 mg/kg i.p.) or glycerol (300, 450, and 600 mg/kg) also significantly suppressed 60-min and 120-min food intake dose dependently in these birds, and equimolar glucose (1,200 mg/kg) had no effect. We conclude that feeding by the white-crowned sparrow is unresponsive to manipulations of carbohydrate metabolism and is decreased after manipulations that increase plasma lipids.
Adrenalectomy decreases NaCl intake of rats fed low-calcium diets
Authors: Tordoff M. G.
Published: December 2017

Five studies were conducted to characterize the effects on NaCl intake of the interaction between adrenalectomy (ADX) and dietary calcium. Intact rats fed low-calcium diets (0 or 25 mmol Ca2+/kg diet) approximately quadrupled intake of 300 or 500 mM NaCl solution relative to intact rats fed diets with moderate or high calcium content (125, 150, or 500 mmol Ca2+/kg diet) ADX approximately doubled NaCl intake of rats fed moderate or high-calcium diets but decreased NaCl intake of rats fed low-calcium diets to levels similar to those of ADX rats fed moderate of high-calcium diets. Aldosterone replacement (2.4 micrograms/day sc) reduced NaCl intake of ADX rats fed control diets to below levels of intact controls, but the same treatment to ADX rats fed low-calcium diet had no effect on NaCl intake. The reduction in NaCl intake produced by ADX in rats fed low-calcium diet could not be attributed to general debilitation, damage to the adrenal medulla, or altered metabolism of sodium or calcium (i.e., plasma concentration, bone content, or balance). It is proposed that an adrenocortical hormone other than aldosterone mediates the high salt intake of the calcium-deprived rat, and thus the adrenal has both inhibitory and excitatory actions on NaCl intake.
Dissociation of hypothalamic NPY from BAT uncoupling protein mRNA in rats exposed to 24 h thermoneutrality
Authors: Bing C. , Frankish H. , Wang Q. , Hopkins D. , Keith J. , Trayhurn P. , Williams G.
Published: December 2017

Neuropeptide Y (NPY) is increasingly considered to be involved in the central regulation of energy balance. Our previous studies suggest that hypothalamic NPY neurons of the arcuatoparaventricular (ARC-PVN) projection are inhibited in association with the marked increases in brown adipose tissue (BAT) thermogenesis and uncoupling protein (UCP) gene expression in rats exposed to cold. We therefore hypothesized that the NPYergic ARC-PVN system would be activated in a thermoneutral environment, when energy expenditure falls to a minimum, and that this activation could mediate the fall in BAT activity. We measured regional hypothalamic NPY concentrations, hypothalamic NPY receptor binding, and NPY mRNA together with UCP mRNA levels in rats exposed to thermoneutrality (29 degrees C) for 24 h. At thermoneutrality, UCP mRNA levels fell to 42% of those in controls maintained at 22 degrees C, but there were no significant changes in hypothalamic NPY or NPY mRNA levels or in NPY receptor binding. We conclude that the fall in UCP mRNA expression occurring under short-term thermoneutral condition is mediated by neuroendocrine mechanisms other than increased activity of hypothalamic NPY neurons.
CO2-sensitive olfactory and pulmonary receptor modulation of episodic breathing in bullfrogs
Authors: Kinkead R. , Milsom W.
Published: December 2017

Breathing was monitored during normocarbia, hypercarbia (6% CO2 in air), and the period immediately after the return to normocarbic conditions in intact, olfactory-denervated, and vagotomized bullfrogs. In intact frogs, ventilation increased during hypercarbia, but the breathing pattern remained episodic. Immediately upon return to air, there was a further paradoxical increase in breathing frequency, and breathing became continuous in most frogs. Results obtained from animals after olfactory receptor denervation indicate that tonic stimulation of olfactory receptors by airway CO2 inhibited breathing during hypercarbia. Measurements of the kinetics of changes in airway and arterial blood CO2 levels support the suggestion that the sudden release of this inhibition on the return to normocarbic conditions was responsible for the posthypercarbic hyperpnea. Vagotomy increased ventilation during normocarbia. Hypercarbia now caused a change in breathing pattern but had no net effect on total ventilation, suggesting that pulmonary vagal feedback inhibited ventilation during normocarbia but stimulated ventilation during hypercarbia. Although olfactory and pulmonary receptor feed-back shape the breathing pattern, they were not responsible for initiating or terminating the episodes of breathing.
Thermoregulatory effects of cyanide and azide in the toad, Bufo marinus
Authors: Branco L. G. , Malvin G. M.
Published: December 2017

An important adaptation to hypoxia is a regulated reduction in body temperature (Tb; anapyrexia), presumably because it lowers metabolic rate when oxygen supply is limited. Although this beneficial response occurs in organisms ranging from protozoans to mammals, little is known of the cellular mechanisms involved. We showed previously that inhibition of oxidative phosphorylation mediates hypoxia-induced anapyrexia in the paramecium. In this study, we tested the hypothesis that inhibition of oxidative phosphorylation also causes anapyrexia in a vertebrate, Bufo marinus. Tb in toads was measured in a thermal gradient 24 h before and 24 h after administration of either NaCN or NaN3, both inhibitors of oxidative phosphorylation. Subcutaneous NaCN (0.6 mmol/kg) reduced Tb from 29.1 +/- 0.8 to 19.6 +/- 0.6 degree C (P = 0.002). Infusion of NaCN (0.6 mumol/kg) into the fourth ventricle of the brain reduced Tb from 30.0 +/- 0.9 to 24.8 +/- 1.2 degrees C (P = 0.01). Responses to NaN3 were similar to the NaCN responses. Control injections and subcutaneous injections of 0.6 mumol/kg NaCN and NaN3 had no significant effect on Tb (P > 0.32). Neither NaCN nor NaN3 had significant effects on arterial PO2, PCO2, or pH at 26 degrees C. These results indicate that inhibition of oxidative phosphorylation in the central nervous system leads to the selection of cooler temperatures. Thus reduced oxidative phosphorylation within the brain may be an important factor eliciting hypoxia-induced anapyrexia.
Diurnal and seasonal changes in sympathetic signal transduction in cardiac ventricles of European hamsters
Authors: Pleschka K. , Heinrich A. , Witte K. , Lemmer B.
Published: December 2017

This investigation of the relationship between cardiac beta-adrenoceptors and adenosine 3',5'-cyclic monophosphate (cAMP) formation in cardiac ventricles of the nocturnally active European hamster both during euthermia under a 12:12-h dark-light cycle and during hibernation under constant-darkness conditions showed that neither the densities, affinities, nor distribution of the beta 1- and beta 2-receptor subtypes differed between the dark phase, light phase, and hibernation. Basal formation of cAMP by the cardiac adenylyl cyclase of euthermic hamsters was higher in ventricles obtained at night [core temperature (Tcore) = 37.8 degrees C] than in ventricles obtained during the day (Tcore = 36.4 degrees C). Basal formation of cAMP was also significantly lower in hibernating hamsters (Tcore = 7.0 degrees C) than in euthermic hamsters. When adenylyl cyclase activity was stimulated by isoprenaline, guanylylimidodiphosphate [Gpp(NH)p], or forskolin, the rank order of potency was the same in euthermic hamsters and hibernating hamsters: isoprenaline < Gpp(NH)p < forskolin. Functional competition curves indicated that in the euthermic hamsters beta 1-receptors were responsible for 67% of the response to isoprenaline at night and 62% of the response during the day. In hibernating hamsters, in contrast, most of the response to isoprenaline (58%) was mediated via beta 2-receptors. This shift in the relative importance of the receptor subtypes may facilitate arousal from hibernation by making the heart more sensitive to circulating epinephrine.
Role of the adrenal glands in the maturation of lung liquid secretory mechanisms in fetal sheep
Authors: Wallace M. J. , Hooper S. B. , Harding R.
Published: December 2017

Our aim was to determine the role of the fetal adrenal glands in the gestational age-related increase in the ability of epinephrine to induce the reabsorption of lung liquid. Fetal lung liquid volumes and secretion rates were measured in five chronically catheterized control and six bilaterally adrenalectomized (ADX) fetal sheep at approximately 5-day intervals from 120 to 144 days of gestation (term approximately 146 days). The ability of epinephrine to induce the reabsorption of fetal lung liquid was then determined on day 144. Fetal adrenalectomy prevented the preparturient increase in fetal plasma cortisol and 3,5,3'-triiodothyronine (T3) concentration and significantly reduced the gestational age-related increase in fetal lung liquid volumes and secretion rates. Close to term (144 days), epinephrine infusions caused a significantly greater rate of lung liquid reabsorption in control (32.2 +/- 4.8 ml/h) compared with ADX (3.7 +/- 0.7 ml/h) fetuses. We conclude that the presence of the fetal adrenal glands is necessary for the age-related increase in 1) the lung liquid secretion rate and 2) the ability of the fetal lung to reabsorb liquid late in gestation. It is likely that cortisol is the active adrenal hormone involved, supporting the theory that cortisol plays a crucial role in the clearance of lung liquid at birth.
Regulation of succinate dehydrogenase within muscle fiber compartments by nerve-mediated activity and CNTF
Authors: Michel R. N. , Campbell R. J. , Jasmin B. J.
Published: December 2017

We investigated the regulatory effects of neural activation and trophic factors on the selective accumulation of succinate dehydrogenase (SDH; EC 1.3.99.1) activity at the endplate, as well as within subsarcolemmal and intermyofibrillar regions of rat soleus muscle fibers. The role of activation was assessed by stimulation of tetrodotoxin (TTX)-inactivated nerves distal to the site of drug application. We also studied whether ciliary neurotrophic factor (CNTF) is involved in regulating the postsynaptic accumulation of SDH. Using quantitative microphotometry, we found that daily stimulation of quiescent but intact nerves prevented the TTX-induced decrease in SDH activity within extrajunctional regions, whereas, at the endplate, the counteraction was partial (30%). Thus it appears that endplate levels of this enzyme are regulated by a complex mechanism involving an interaction between neuromuscular activation and trophic factors. We also found that daily CNTF administration counteracted the denervation-associated loss of SDH activity exclusively within the intermyofibrillar compartment, suggesting that CNTF treatment mimics the effects of activity on SDH levels within the core region of denervated fibers, but under these conditions does not influence the endplate accumulation of this enzyme.
Roles of IL-1 and TNF-alpha in endotoxin-induced activation of nitric oxide synthase in cultured rat brain cells
Authors: Romero L. I. , Tatro J. B. , Field J. A. , Reichlin S.
Published: December 2017

In astrocytes and microglia, bacterial lipopolysaccharide (LPS) stimulates production and release of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO). Although IL-1 beta and TNF-alpha are themselves capable of inducing NO synthase (NOS) in glia, the specific factors mediating LPS induction of NOS in brain have not been identified. To determine whether LPS induction of NOS in brain cells is mediated by IL-1 or TNF-alpha, acting alone or in concert, the effects of IL-1-receptor antagonist (IL-1Ra) and of TNF-soluble receptor (TNFsRp55), presented individually and in combination, on LPS-induced NOS activity were tested. In glial-enriched mixed primary cultures of neonatal rat telencephalic cells, LPS (0.1-100 ng/ml), IL-1 beta (0.01-10 nM), and TNF-alpha (0.1-100 nM) each concentration dependently stimulated accumulation of nitrite, an indicator of NO production. Induction of nitrite accumulation by LPS and by IL-1 was blocked by N omega-nitro-L-arginine methyl ester and N omega-monomethyl-L-arginine, indicating that it was mediated by NOS. TNF-alpha alone induced NO production weakly as compared with IL-1, but combined submaximal concentrations of IL-1 beta (1 nM) and TNF-alpha (10 nM) induced NOS synergistically. Furthermore, TNFsRp55 and IL-1Ra each produced a dose-dependent partial inhibition of the NO response to LPS, and the effect of TNFsRp55 was equal to or greater than that of IL-1Ra. TNFsRp55 and IL-1Ra in combination were not significantly more effective than TNF-sRp55 alone. The results indicate that LPS induction of NOS activity in brain cells is mediated in part by both IL-1 beta and TNF-alpha.
Glucoprivation counteracts effects of testosterone on daily torpor in Siberian hamsters
Authors: Dark J. , Miller D. R. , Licht P. , Zucker I.
Published: December 2017

We tested whether 1) glucose availability is a signal for initiation of torpor in male hamsters and 2) glucoprivation can override the inhibitory effects of androgens on daily torpor. Male hamsters maintained at ambient temperatures of 8-16 degrees C were injected with 2-deoxy-D-glucose (2DG), a glucose analogue that interferes with cellular glucose oxidation. 2DG (2,000-2,500 mg/kg body mass) induced torpor within 1 h of treatment in normal adult males in reproductive condition and in those bearing testosterone (T)-filled capsules that produced supraphysiological blood T concentrations; body temperatures were reduced from 37 to 25 degrees C for several hours. Latency to torpor was increased and duration of torpor was decreased in the T-treated hamsters. Food intake decreased substantially both on the day of torpor and on the succeeding day. Glucoprivation appears to counteract the potent inhibitory effect of androgens on torpor and induces a hypometabolic state that results in overall energy savings.
Effect of aging on rat skeletal muscle beta-AR function in male Fischer 344 x brown Norway rats
Authors: Larkin L. M. , Halter J. B. , Supiano M. A.
Published: December 2017

In this study, we tested the hypothesis that, in the male Fischer 344 x Brown Norway (F344xBN) rat, aging would be associated with an increase in sympathetic nervous system activity and a decrease in skeletal muscle beta-adrenergic-receptor (beta-AR) density and function. Radioligand-binding studies using [125I] iodocyanopindolol were done to evaluate beta-AR density (Bmax) and antagonist-binding affinity in gastrocnemius and cardiac muscle from 6-, 18-, and 28-mo-old male F344xBN rats. beta-AR function was measured as adenylyl cyclase (AC) activity stimulated by the beta-AR agonist isoproterenol (Iso, 10(-4) M). Basal arterial plasma norepinephrine (pNE) concentrations were higher in the 28-than in the 6- and 18-mo-old rats. Bmax was greatest and Iso-stimulated AC activity was unchanged in gastrocnemius muscle of the 28-mo-old age group. In contrast, there was an age-associated decrease in Bmax and Iso-stimulated AC activity in cardiac muscle. In conclusion, there was an age-associated increase in pNE concentrations in male F344xBN rats, suggesting an increase in sympathetic nervous system activity. In addition, there was an age-associated increase in skeletal muscle beta-AR density, whereas in skeletal muscle beta-AR-stimulated AC activity remained unchanged with age.
Pressure natriuresis following acute and chronic inhibition of nitric oxide synthase in rats
Authors: Guarasci G. R. , Kline R. L.
Published: December 2017

Nitric oxide has been suggested to be an essential mediator of pressure natriuresis. To investigate this hypothesis, the effect of acute or chronic inhibition of nitric oxide synthase on pressure natriuresis and renal interstitial hydrostatic pressure was studied in anesthetized Sprague-Dawley rats with fixed neural and hormonal influences on the kidney. Both acute infusion (10 micrograms.kg-1.min-1 iv) and chronic administration (50 mg.kg-1.day-1 for 7 days in drinking water) of NG-nitro-L-arginine methyl ester (L-NAME) resulted in significantly increased mean arterial pressure, a 30% decrease in renal blood flow, and no change in glomerular filtration rate when compared with values in control rats. Pressure-diuresis, pressure-natriuresis, and pressure-fractional sodium excretion curves in L-NAME-treated rats were shifted to a higher pressure (by approximately 25 mmHg) when compared with those in control rats. The relationship between renal artery pressure and renal interstitial hydrostatic pressure was shifted similarly in L-NAME-treated rats. Acute administration of L-arginine completely reversed the renal effects of chronic L-NAME. These data indicate that, at the doses used in this study, both acute and chronic inhibition of nitric oxide synthase decreased the ability of the kidney to excrete sodium at least in part by a hemodynamic mechanism leading to an increased filtration fraction and a decreased renal interstitial pressure. The parallel shift of the pressure-natriuresis curve to a higher pressure suggests that nitric oxide is an important modulator but not an essential mediator of the pressure natriuresis.
Renal sensory receptor activation causes prostaglandin-dependent release of substance P
Authors: Kopp U. C. , Farley D. M. , Smith L. A.
Published: December 2017

Renal mechanoreceptor (MR) activation by increased ureteral pressure (increases UP) results in an increase in afferent renal nerve activity (ARNA) that is blocked by substance P receptor blockade and prostaglandin (PG) synthesis inhibition. To examine the interaction between substance P and PGs, the release of substance P and PGE into the renal pelvis was studied before and during renal pelvic perfusion with indomethacin. Before indomethacin, increases UP increased ARNA 43 +/- 6% and renal pelvic release of substance P from 11 +/- 3 to 29 +/- 8 pg/min and PGE from 319 +/- 71 to 880 +/- 146 pg/min. Indomethacin blocked the increases in ARNA and release of substance P and PGE produced by increases UP. Time control experiments showed reproducible increases in ARNA and release of substance P and PGE during increases UP. Mechanical stimulation of the renal pelvic wall in vitro resulted in an increase in PGE release from 110 +/- 8 to 722 +/- 152 pg/min, which was abolished by indomethacin, suggesting a de novo PGE synthesis. The data suggest that increases UP results in a renal pelvic release of PGE, which facilitates the release of substance P and activation of renal pelvic MR.