bluuebunny/crossref_metadata_2025 huggingface dataset:
The area postrema does not modulate the long-term salt sensitivity of arterial pressure
Authors: Collister John P. , Osborn John W.
Published: December 2017

The hindbrain circumventricular organ, the area postrema (AP), receives multiple signals linked to body fluid homeostasis. In addition to baroreceptor input, AP cells contain receptors for ANG II, vasopressin, and atrial natriuretic peptide. Hence, it has been proposed that the AP is critical in long-term adjustments in sympathetic outflow in response to changes in dietary NaCl. The present study was designed to test the hypothesis that long-term control of arterial pressure over a range of dietary NaCl requires an intact AP. Male Sprague-Dawley rats were randomly selected for lesion of the AP (APx) or sham lesion. Three months later, rats were instrumented with radiotelemetry transmitters for continuous monitoring of mean arterial pressure (MAP) and heart rate and were placed in individual metabolic cages. Rats were given 1 wk postoperative recovery. The dietary salt protocol consisted of a 7-day period of 1.0% NaCl (control), 14 days of 4.0% NaCl (high), 7 days of 1.0% NaCl, and finally 14 days of 0.1% NaCl (low). The results are reported as the average arterial pressure observed on the last day of the given dietary salt period: APx ( n = 7) 114 ± 2 (1.0%), 110 ± 3 (4.0%), 110 ± 3 (1.0%), and 114 ± 4 (0.1%) mmHg; sham ( n = 6) 115 ± 2 (1.0%), 114 ± 3 (4.0%), 111 ± 3 (1.0%), and 113 ± 2 (0.1%) mmHg. Neither group of rats demonstrated significant changes in MAP throughout the entire dietary salt protocol. Furthermore, no significant differences in MAP were detected between groups throughout the protocol. All lesions were histologically verified. These results suggest that the area postrema plays no role in long-term control of arterial pressure during chronic changes in dietary salt.
N-acetylcysteine does not affect the lymphocyte proliferation and natural killer cell activity responses to exercise
Authors: Nielsen H. B. , Secher N. H. , Kappel M. , Pedersen B. K.
Published: December 2017

This study evaluated whether N-acetylcysteine (NAC) attenuates the reduced lymphocyte proliferation and natural killer (NK) cell activity responses to exercise in humans. Fourteen oarsmen were double-blind randomized to either NAC (6 g daily for 3 days) or placebo groups. During 6-min “all-out” ergometer rowing, the concentration of lymphocytes in the peripheral blood increased, with no significant difference between NAC and placebo as reflected in lymphocyte subsets: CD4+, CD8+, CD16+, and CD19+cells. The phytohemagglutinin-stimulated lymphocyte proliferation decreased from 9,112 ± 2,865 to 5,851 ± 1,588 cpm ( P < 0.05), but it was not affected by NAC. During exercise, the NK cell activity was elevated from 17 ± 3 to 38 ± 4% and it decreased to 7 ± 1% below the resting value 2 h into recovery. Yet, when evaluated as lytic units per CD16+cell, the NK cell activity decreased during and after exercise without a significant effect of NAC. We conclude that NAC does not attenuate the reduction in lymphocyte proliferation and NK cell activity associated with intense exercise.
Myostatin expression in porcine tissues: tissue specificity and developmental and postnatal regulation
Authors: Ji Shaoquan , Losinski R. L. , Cornelius S. G. , Frank G. R. , Willis G. M. , Gerrard D. E. , Depreux F. F. S. , Spurlock M. E.
Published: December 2017

The objective of this study was to establish the developmental pattern and tissue specificity of porcine myostatin expression and to evaluate expression in skeletal muscle during circumstances in which muscle growth was altered. Northern blot analysis revealed two transcripts (1.5 and 0.8 kb). Myostatin mRNA was detected in whole fetuses at 21 and 35 days and was markedly increased ( P < 0.05) by 49 days. At birth, mRNA abundance in longissimus muscle had declined significantly ( P < 0.05) from that at day 105 of gestation and continued to decrease ( P < 0.05) to its lowest level 2 wk postnatally (4 kg body wt). Myostatin expression was higher ( P < 0.05) at 55, 107, and 162 kg body wt than at 4 kg body wt. Postnatally, myostatin mRNA was detected in skeletal muscle and mammary gland. Expression at birth was 65% higher ( P < 0.04) in longissimus muscle of low-birth-weight piglets (0.57 ± 0.052 kg body wt) vs. normal (1.37 ± 0.077 kg body wt) littermates, irrespective of gender. However, suppression of longissimus muscle growth by food deprivation (3 days) did not alter ( P > 0.15) myostatin expression in either 4- or 7-wk-old piglets. Additionally, myostatin mRNA abundance was not changed by porcine growth hormone administration in growing animals. These data indicate that myostatin expression in skeletal muscle peaks prenatally and that greater expression is associated with low birth weight. Expression in mammary gland indicates a possible role for myostatin in mammary gland development and/or lactation.
Sympathetic nerve activity during natural stimulation of horizontal semicircular canals in humans
Authors: Ray Chester A. , Hume Keith M. , Steele Samuel L.
Published: December 2017

We have shown that static head-down neck flexion elicits increases in muscle (MSNA) but not skin sympathetic nerve activity (SSNA) in humans. These findings suggest that stimulation of the otolith organs causes differential sympathetic outflow to vascular beds. The purpose of the present study was to determine whether yaw head rotation (YHR), which stimulates the horizontal semicircular canals, elicits sympathetic nerve responses. To test this question, we recorded MSNA ( n = 33) and SSNA ( n = 25) before and during 3 min of sinusoidal YHR performed at 0.1, 0.6, and 1.0 Hz. At all frequencies, YHR elicited no significant changes in heart rate and mean arterial pressure. Likewise, YHR did not significantly change either MSNA or SSNA at all frequencies. Our results indicate that stimulation of the horizontal semicircular canals by YHR does not alter SNA to either muscle or skin. Moreover, these results provide evidence to support the concept that the otolith organs but not the horizontal semicircular canals participate in the regulation of SNA in humans.
Length of intestinal contact on nutrient-driven satiety
Authors: Meyer J. H. , Tabrizi Y. , DiMaso N. , Hlinka M. , Raybould H. E.
Published: December 2017

Chemosensors throughout small bowel and colon inhibit food intakes when contacted by monomeric nutrients. We postulated that calorie-dependent inhibition of food intakes depended on additions of feedbacks from sensors in proximal and distal bowel contacted after high intakes of nutrients. Therefore, we determined how feedback from sensors in proximal gut interacted with feedback from simultaneously contacted sensors in distal bowel and whether suppression of nutrient intakes by intestinally perfused nutrients depended on length of gut contacted. Suppression of food intakes by maltose simply added to that from dodecanoate when both were present together either in proximal or distal small bowel. When dodecanoate was infused into proximal gut while maltose was infused distally, suppression of intake was threefold higher and was thus potentiated. Limiting contact of slowly absorbed lactose or oleate to 35 cm of jejunum nearly abolished the satiating potencies each exhibited during access to whole gut. The observations were consistent with our hypothesis.
Gestational obesity accentuates obesity in obesity-prone progeny
Authors: Levin Barry E. , Govek Elizabeth
Published: December 2017

Maternal obesity and genetic background can affect the development of obesity and diabetes in offspring. Here we used selected strains of rats resistant (DR) vs. susceptible to development of diet-induced obesity (DIO) on high-energy (HE) diets to assess this issue. DR and DIO dams were fed either Chow or HE diet for 4 wk. DIO HE diet-fed dams and additional DR rats fed a palatable liquid diet (Ensure) became more obese and hyperinsulinemic than the other groups. During lactation, all dams were fed their respective diets, and offspring were fed Chow from weaning to 16 wk of age. All offspring of DIO dams gained more weight and had heavier retroperitoneal fat pads and higher leptin levels than DR progeny, but offspring of the more obese DIO HE dams had heavier fat pads and higher glucose levels than DIO Chow offspring. After 4 wk on HE diet, all DIO offspring gained more weight and had heavier total adipose depots and higher insulin and leptin levels than DR offspring. Offspring of DIO HE dams also gained more weight and had heavier fat depots and higher leptin levels than DIO Chow offspring. Therefore maternal obesity and hyperinsulinemia were associated with increased obesity in those offspring already genetically predisposed to become obese.
Effects of aortic nerve stimulation on discharges of sympathetic neurons innervating rat tail artery and vein
Authors: Johnson Christopher D. , Gilbey Michael P.
Published: December 2017

Activity was recorded from postganglionic sympathetic neurons (PSNs) innervating either the caudal ventral artery (CVA) or a lateral vein (LV) of the tail circulation of anesthetized rats. The study sought to determine whether sympathetic activity directed at the CVA and LV was influenced by cardiovascular mechanoreceptor afferents and whether this effect was differential. Cardiac rhythmicity was not a robust component of either CVA PSN activity or LV PSN activity. Stimulation of an aortic nerve with short trains was followed by a decreased probability of discharge in both CVA and LV PSNs that was followed by a series of peaks that showed a constant periodicity that was not significantly different from that revealed by autocorrelogram analysis over the same data set. The latter dominant periodicity is referred to in this and related previous publications as the T rhythm. Furthermore, blood volume expansion and long-train aortic nerve stimulation produced a significant decrease in the frequency of the T rhythm. It is concluded that the CVA and LV sympathetic activity can be influenced by inputs from cardiovascular mechanoreceptors and that this effect is mediated in part by a modulation of the T rhythm.
Efficacy of exogenous recombinant murine leptin in lean and obese 10- to 12-mo-old female CD-1 mice
Authors: Pelleymounter Mary Ann , Cullen Mary Jane , Healy Denis , Hecht Randy , Winters Dwight , McCaleb Michael
Published: December 2017

Leptin efficacy was compared in obese and lean female CD-1 mice. Body weights in these 10- to 12-mo-old mice ranged from 29.7 to 62.0 g, and leptin levels correlated with body weight. Mice from the lean and obese ends of the weight distribution were treated with daily peripheral leptin injections (1–100 mg/kg) for a 33-day period. The half-maximal effective doses for weight loss and fat reduction were shifted 0.5–0.7 log to the right for obese mice. Leptin was less efficacious at low doses (1–3 mg/kg) in obese mice but equal to or more efficacious in obese than lean mice at high doses (30–100 mg/kg). Leptin’s initial effects on weight loss could be explained by appetite suppression in both groups, but its effects on fat reduction were greater in leptin-treated than pair-fed mice, particularly in the lean group. Leptin also prevented the elevations in serum corticosterone and ketones found in pair-fed lean mice. These data allow a quantitative comparison of leptin sensitivity in obese vs. lean CD-1 mice and suggest that in mice where obesity is a function of outbreeding and age, leptin sensitivity is moderately reduced. Furthermore, although appetite suppression has a clear role in leptin’s effects on body weight, leptin may also have specific effects on lipid metabolism and mobilization that are different from the metabolic compensations that normally occur with food deprivation.
Akt1 kinase and dynamics of insulin resistance in denervated muscles in vivo
Authors: Turinsky Jiri , Damrau-Abney Alice
Published: December 2017

Basal and insulin-stimulated activity of Akt1 kinase and uptake of 2-deoxy-d-glucose (2-DG) were measured in soleus (slow-twitch) and plantaris (fast-twitch) muscles of rats at 1 and 3 days after sectioning the sciatic nerve in one hindlimb of the animals. At 1 day after surgery, the insulin-stimulated activity of Akt1 kinase in denervated soleus and plantaris muscles remained unchanged, but the insulin-stimulated 2-DG uptake by these muscles was reduced by 71 and 61%, respectively, compared with the corresponding muscles of the contralateral sham (control) hindlimb. At 3 days, the insulin-stimulated activity of Akt1 kinase in the denervated soleus and plantaris muscles was 86 and 71% lower, respectively, than in their sham counterparts. At this time point, the denervated soleus muscles showed no increase in 2-DG uptake in response to insulin. In contrast, the denervated plantaris muscle exhibited the same absolute level of insulin-stimulated 2-DG uptake as the sham plantaris muscle; however, the insulin-induced increment in 2-DG uptake was reduced by 60%, whereas basal 2-DG uptake was increased by 251% compared with the sham plantaris muscle. None of the denervated muscles showed a decrease in the abundance of Akt1 kinase. The results demonstrate that the causes of insulin resistance in denervated muscles are dependent on time after surgery. Initially, they involve only mechanisms downstream of Akt1 kinase ( day 1), whereas at day 3 they also involve mechanisms upstream of, and including, Akt1 kinase.
Interleukin-1β fever in rats: gender difference and estrous cycle influence
Authors: Mouihate A. , Chen X. , Pittman Q. J.
Published: December 2017

Evidence exists to support the concept of sex difference in immune system activation by pyrogenic cytokines. In this study, fever development was monitored to analyze the effect of peripheral administration of interleukin (IL)-1β (1 μg/kg) in adult male and cycling or ovariectomized female rats with or without ovarian hormonal replacement. In male and randomly cycling female rats, a similar increase in body temperature occurred after intraperitoneal IL-1β injection. Two representative stages of estrus with higher and lower levels of ovarian hormones (proestrus and diestrus, respectively) were chosen for study of the febrile response induced by IL-1β. The fever induced by IL-1β was found to be significantly higher and more prolonged in females at proestrus than at diestrus. The differential fever response seems to be mainly linked to the ovarian hormonal levels because bilaterally ovariectomized females, supplemented with sequential injections of estradiol 17β and progesterone, showed a significantly higher IL-1β fever than did ovariectomized rats receiving estradiol 17β only. These results indicate that gonadal hormones can influence fever development and raise the possibility of interaction between sex hormones and thermogenesis in females during the estrous cycle.
Peripheral corticotropin-releasing factor mediates the elevation of plasma IL-6 by immobilization stress in rats
Authors: Ando Tetsuya , Rivier Jean , Yanaihara Hitoshi , Arimura Akira
Published: December 2017

We previously reported the elevation of plasma interleukin (IL)-6 activity in response to immobilization stress in rats. To investigate the role of peripheral corticotropin-releasing factor (CRF) in this response, we examined the effects of CRF antagonists on immobilization-induced IL-6 response. Intravenous pretreatment with either [d-Phe12,Nle21,38,CαMeLeu37]-anti-human rat (h/r) CRF12—41(1.5 mg/kg) or cyclo(30—33)[d-Phe12, Nle21,38,Glu30,Lys33]-h/rCRF12—41(Astressin, 0.5 mg/kg) attenuated the IL-6 response to immobilization, which confirmed our previous finding that systemic administration of an antiserum against CRF blocked this response. In addition, an intraperitoneal injection of h/rCRF (100 μg/kg) or rat urocortin (10 and 100 μg/kg) increased the plasma IL-6 activity, mimicking the response to immobilization. An intravenous injection of h/rCRF (100 μg/kg) also elevated plasma IL-6 in adrenalectomized rats. These findings suggest that peripheral CRF mediates the plasma IL-6 elevation in response to immobilization.
Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat
Authors: Powers Scott K. , Demirel Haydar A. , Vincent Heather K. , Coombes Jeff S. , Naito Hisashi , Hamilton Karyn L. , Shanely R. Andrew , Jessup James
Published: December 2017

Experimental studies examining the effects of regular exercise on cardiac responses to ischemia and reperfusion (I/R) are limited. Therefore, these experiments examined the effects of endurance exercise training on myocardial biochemical and physiological responses during in vivo I/R. Female Sprague-Dawley rats (4 mo old) were randomly assigned to either a sedentary control group or to an exercise training group. After a 10-wk endurance exercise training program, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was achieved by a ligature around the left coronary artery; occlusion was maintained for 20 min, followed by a 10-min period of reperfusion. Compared with untrained, exercise-trained animals maintained higher ( P < 0.05) peak systolic blood pressure throughout I/R. Training resulted in a significant ( P < 0.05) increase in ventricular nonprotein thiols, heat shock protein (HSP) 72, and the activities of superoxide dismutase (SOD), phosphofructokinase (PFK), and lactate dehydrogenase. Furthermore, compared with untrained controls, left ventricles from trained animals exhibited lower levels ( P < 0.05) of lipid peroxidation after I/R. These data demonstrate that endurance exercise training improves myocardial contractile performance and reduces lipid peroxidation during I/R in the rat in vivo. It appears likely that the improvement in the myocardial responses to I/R was related to training-induced increases in nonprotein thiols, HSP72, and the activities of SOD and PFK in the myocardium.
Reduced GABA inhibition of sympathetic function in renal-wrapped hypertensive rats
Authors: Martin Douglas S. , Haywood Joseph R.
Published: December 2017

Animals with bilateral cannulas in the paraventricular nucleus were made hypertensive by a one-kidney, figure eight renal wrap procedure or sham operated. Femoral artery and vein catheters were inserted for arterial pressure measurement and plasma catecholamine determination. After recovery and 4 days after hypertension surgery, bicuculline methiodide or muscimol was microinjected into the paraventricular nucleus. In some rats, nitroprusside was infused intravenously to reflexly stimulate the sympathetic nervous system. In control rats, bicuculline increased blood pressure, heart rate, and plasma norepinephrine and epinephrine concentrations. In contrast, in hypertensive rats blood pressure did not change while the heart rate response was maintained. Plasma norepinephrine and epinephrine responses were reduced 75 and 68%, respectively. Muscimol injections decreased arterial pressure in the hypertensive rats. Heart rate responses to nitroprusside were similar in the two groups of rats, while the plasma catecholamine responses were attenuated in the hypertensive animals. These data suggest that GABA function in the paraventricular nucleus is reduced in renal wrap hypertension.
Shivering thermogenesis in the pigeon: the effects of activity, diurnal factors, and feeding state
Authors: Hohtola Esa , Henderson Ross P. , Rashotte Michael E.
Published: December 2017

Shivering (electromyographic activity of the pectoral muscle), oxygen consumption, and body temperature were measured from undisturbed pigeons for periods of several weeks, and segments from the midparts of each phase of the light-dark cycle were compared at various ambient temperatures and feeding regimes. Behavior was recorded with a video camera. None of the observed types of behavior (e.g., walking, preening, feeding, drinking, pecking, defecation) induced spurious electrical activity in the pectoral muscle. On the other hand, none of these behaviors directly inhibited ongoing shivering. There was no difference in the mean level of shivering between the light (L) and dark (D) phases of the day in any of the conditions, although body temperature was 2°C higher during L. Measurements of integrated electromyogram (EMG) with high temporal resolution (28 samples/s) showed that, at 1°C, shivering in the pectoral muscle was present for more than 98% of the time. Plots of oxygen consumption against root mean square EMG were obtained in each condition by a filtering procedure that excludes data points in which oxygen consumption is affected by motor activity. These plots showed that the increase in heat production induced by a unit increase in pectoral EMG was lower in D than in L and that it was further lowered by fasting. The amplitude spectra of raw EMG signals were similar in all conditions. Spectra of demodulated (rectified, low-pass filtered) EMG showed a distinct rhythmicity around 8 Hz at 21°C that was further enhanced by fasting but absent at 1°C. This suggests that the degree of synchronization and pattern of recruitment of motor units are specific for various temperatures and feeding regimes, and may partly explain the variable relation between heat production and muscle electrical activity. The results emphasize the advantages of long-term measurements for understanding the control of thermogenesis in birds.
Adenylyl cyclase activity and glucose release from the liver of the European eel,Anguilla anguilla
Authors: Fabbri Elena , Barbin Laura , Capuzzo Antonio , Biondi Carla
Published: December 2017

The properties of adenylyl cyclase (AC) in liver membranes of the European eel ( Anguilla anguilla) and the involvement of cAMP in glucose release from isolated hepatocytes in response to catecholamines were studied. Basal enzyme activity seemed essentially unaffected by GTP, while a biphasic response to increasing nucleotide concentrations was obtained in the presence of epinephrine. Eel liver AC was dose-dependently stimulated by guanosine 5′- O-(3-thiotriphosphate) and inhibited by guanosine 5′- O-(2-thiodiphosphate). AC activity, intracellular cAMP levels, and glucose release from isolated hepatocytes were significantly enhanced by NaF, forskolin, epinephrine, and phenylephrine. The rise in cAMP production stimulated by catecholamines was counteracted by propranolol, but not by phentolamine. Catecholamine-induced glucose output was instead partially antagonized by both phentolamine and propranolol. Complete inhibition was obtained only by the simultaneous presence of the two adrenergic antagonists. Glucose release from the cells was induced by dibutyryl cAMP and by the calcium ionophore ionomycin. In summary, these data provide the first characterization of eel liver AC system and suggest a direct role for cAMP in the catecholamine-dependent glucose output. Furthermore, the involvement of calcium ions in this cellular response is hypothesized.
Gender difference in flow-induced dilation and regulation of shear stress: role of estrogen and nitric oxide
Authors: Huang An , Sun Dong , Koller Akos , Kaley Gabor
Published: December 2017

Previous studies show that agonist-induced, nitric oxide (NO)-mediated arteriolar dilations are greater in female than in male rats. Thus we hypothesized that flow-dependent arteriolar dilation, which is in part mediated by NO, is also greater in females than in males. Gracilis muscle arterioles from 12-wk-old female and male Wistar rats were isolated, cannulated, and pressurized. At 80 mmHg of perfusion pressure, the active diameter and passive diameter (PD) of arterioles of female and male rats were 58.3 ± 3.4 and 53.2 ± 2.6 μm as well as 103.6 ± 4.0 and 115.3 ± 4.8 μm, respectively. Dilations to step increases in perfusate flow from 0 to 25 μl/min were significantly greater in arterioles of female rats and ovariectomized rats with estrogen replacement (OVE) than in male and ovariectomized female (OV) rats (98.6 ± 0.6 and 97.4 ± 1.1% vs. 72.6 ± 3.3 and 72.5 ± 3.6% of PD at 25 μl/min). Calculation of wall shear stress (WSS) revealed that the maintained WSS was significantly lower in arterioles of female than in those of male rats (∼20 vs. ∼35 dyn/cm2). After indomethacin pretreatment, N ω-nitro-l-arginine methyl ester (l-NAME; 10−4 M) eliminated flow-dependent dilation in arterioles of male and OV rats but only attenuated (by ∼50%) the responses in arterioles of female and OVE rats. In vessels of these latter two groups of rats, the remaining flow-induced dilation was completely eliminated by administration of 10−5 M Hb or 10−3 Ml-NAME. The greater flow/shear stress-induced dilation of arterioles of female rats indicates a gender difference in the regulation of WSS, which is likely to be due to the greater release of NO in female vessels requiring the chronic presence of estrogen. These findings suggest an important role for estrogen in the regulation of peripheral resistance in females.
Daily rhythms in Fos activity in the rat ventrolateral preoptic area and midline thalamic nuclei
Authors: Novak Colleen M. , Nunez Antonio A.
Published: December 2017

The present experiment investigated the expression of the nuclear phosphoprotein Fos over the 24-h light-dark cycle in regions of the rat brain related to sleep and vigilance, including the ventrolateral preoptic area (VLPO), the paraventricular thalamic nucleus (PVT), and the central medial thalamic nucleus (CMT). Immunocytochemistry for Fos, an immediate-early gene product used as an index of neuronal activity, was carried out on brain sections from rats perfused at zeitgeber time (ZT) 1, ZT 5, ZT 12.5, and ZT 17 (lights on ZT 0–ZT 12). The number of Fos-immunopositive (Fos+) cells in the VLPO was elevated at ZT 5 and 12.5 (i.e., during or just after the rest phase of the cycle). Fos+cell number increased at ZT 17 and ZT 1 in the PVT and CMT, 180° out of phase with the VLPO. A positive correlation was found between the numbers of Fos+ cells in the PVT and CMT, and Fos expression in each thalamic nucleus was negatively correlated with VLPO Fos+ cell number. The VLPO, PVT, and CMT may integrate circadian and homeostatic influences to regulate the sleep-wake cycle.
Leptin increases energy expenditure of a marsupial by inhibition of daily torpor
Authors: Geiser Fritz , Körtner Gerhard , Schmidt Ingrid
Published: December 2017

Leptin plays an important role in regulating body fat stores of placental mammals, but the contribution of changes in energy expenditure to this adjustment remains controversial. We were interested in how recombinant murine leptin would affect metabolic rate (MR) and body temperature (Tb) of a marsupial mammal ( Sminthopsis macroura, 25 g) known to display daily torpor but lacking thermogenetically active brown adipose tissue. In a group of eight animals deprived of food for 1 day at 18°C, leptin treatment halved the duration of torpor bouts (time at Tb< 30°C) and raised the average daily minimum Tbby 4.5°C and minimum MR by 2.2-fold. Leptin treatment thus increased daily energy expenditure by 9%, although MR and Tbduring the activity phase were not raised. Body mass was also not affected. These findings in a marsupial suggest that the adjustment of thermoregulatory energy expenditure during the rest phase in accordance with energy availability is a phylogenetically old function of leptin.
Correlation integral of blood pressure as a marker for exercise intensities
Authors: Wagner C. D. , Stauss H. M. , Persson P. B. , Kregel K. C.
Published: December 2017

The purpose of this study was to test the hypothesis that the correlation integral technique detects altered regulation of cardiovascular function during graded treadmill exercise. Arterial blood pressure (BP) was measured via telemetry before and during graded treadmill exercise in Sprague-Dawley rats. During treadmill running at mild, moderate, and heavy exercise intensities, the slope of the correlation integrals (SCI) continuously increased from 5.45 ± 0.17 to 7.12 ± 0.18, 7.92 ± 0.23, and 8.40 ± 0.23, respectively. However, corresponding changes in pulse interval, blood pressure, and systolic blood pressure with increasing workload were not consistently observed. Low-frequency, midfrequency, and high-frequency powers of BP were not different between adjacent exercise grades; only the low-frequency component of pulse interval was different between resting state and mild exercise, and BP variance was significantly different between mild and moderate grades. Comparison of the SCI values with those obtained from surrogate data sets suggests that these differences originate mainly from nonlinear components in the cardiovascular control system. These findings support the hypothesis that SCI detects alterations in cardiovascular regulation associated with graded exercise. Furthermore, SCI may be superior to linear techniques in detecting altered regulation with changing exercise intensities.
Vigilance states and body temperature during the circadian cycle in fed and fasted pigeons (Columba livia)
Authors: Rashotte Michael E. , Pastukhov Iuri F. , Poliakov Eugene L. , Henderson Ross P.
Published: December 2017

Fasting induces nocturnal hypothermia in pigeons. Slow-wave sleep (SWS) and paradoxical sleep (PS) are associated with reduced heat production in pigeons. The possibility that fasting-induced nocturnal hypothermia is related to increased SWS and PS was examined by comparing body temperature (Tb) and vigilance states when pigeons were fed and fasted. The results showed that when Tb is decreasing near the beginning of the dark phase, the percentage of total recording time (%TRT) spent in SWS and PS was elevated in fasting due to increased frequency of episodes and increased duration of PS episodes. When Tb was low during the middle segment of the dark phase, SWS was elevated in fasting due to increased episode duration. However, fasting did not alter PS, which increased in %TRT across the segment due to increased episode frequency. When Tb was rising during the final hours of dark, SWS remained elevated in fasting and %TRT in SWS and PS was relatively high. SWS and PS may promote the fasting pigeon’s entry into, and maintenance of, nocturnal hypothermia.
Hypertensive response to chronic NO synthase inhibition is different in Sprague-Dawley rats from two suppliers
Authors: Pollock David M. , Rekito Anthony
Published: December 2017

Experiments were conducted to determine whether Sprague-Dawley rats from different suppliers have the same hypertensive response to chronic inhibition of nitric oxide synthase. Rats (240–260 g) obtained from either Harlan or Charles River Laboratories were maintained in metabolic cages for baseline ( week 0) measurements before receiving Nω-nitro-l-arginine methyl ester (l-NAME) in the drinking water for 2 wk at 5 or 65 mg ⋅ kg−1⋅ day−1. Baseline values for tail cuff pressure (TCP) were significantly higher in Harlan rats (131 ± 2 mmHg) compared with Charles River rats (108 ± 3 mmHg, P < 0.001). At 65 mg ⋅ kg−1⋅ day−1,l-NAME produced a significantly larger increase in TCP in Harlan versus Charles River rats (41 ± 4 vs. 29 ± 4%, respectively, P < 0.01). Food and water intake and sodium and water excretion were not different between groups. Urinary excretion of nitrate and nitrite ([Formula: see text]V) was significantly reduced in all rats givenl-NAME.[Formula: see text]V was decreased by 69 ± 12 and 62 ± 7% in Harlan and Charles River rats, respectively. The lower dose ofl-NAME increased TCP and decreased [Formula: see text]V in both Harlan and Charles River rats; these effects were more pronounced in the Harlan rats. These results suggest that NO plays a more significant role in the maintenance of arterial pressure in Sprague-Dawley rats from Harlan compared with Charles River Laboratories. Such findings may also provide insight as to why some of the mechanisms associated with chronicl-NAME treatment are not consistent between laboratories.
PGE2, via EP3receptors, regulates brain nitric oxide synthase in the perinatal period
Authors: Dumont Isabelle , Peri Krishna G. , Hardy Pierre , Hou Xin , Martinez-Bermudez Ana Katherine , Molotchnikoff Stéphane , Varma Daya R. , Chemtob Sylvain
Published: December 2017

We tested the hypothesis that high prostaglandin levels during the perinatal period might regulate brain nitric oxide synthase (nNOS) expression. nNOS and cyclooxygenase (COX)-2 mRNAs were higher in brain cortex and the periventricular area of newborn rats and pigs compared with adult brain. Nitric oxide synthase activity was also 2.5- to 4-fold higher in newborn than in adult brain. Administration of nonselective COX inhibitor ibuprofen or COX-2 inhibitor nimesulide every 8 h for 24 h to newborn rats and pigs reduced prostaglandin levels and caused comparable reductions in nNOS mRNA, protein, and activity to levels of adults; COX inhibitor-induced changes were prevented by cotreatment with PGE2analog, 16,16-dimethyl-PGE2, and agonist for the EP3receptor of PGE2, sulprostone, but not by PGI2analog carbaprostacyclin, PGD2, EP1receptor agonist 17-phenyl trinor-PGE2, and EP2agonist butaprost. Concordant observations were made in vitro and revealed that nNOS expression (detected by NADPH diaphorase reactivity) mostly present in neurons of the deeper cortical layers was reduced by COX inhibitor, and this effect was prevented by EP3agonist. In conclusion, high levels of PGE2in neonatal brain contribute to the increased expression of nNOS by acting on EP3receptors; this positive interaction between PGE2and nNOS might be required physiologically for normal brain development.
Vasoconstrictor actions of atrial natriuretic peptide in the splanchnic circulation of anesthetized dogs
Authors: Woods Robyn L.
Published: December 2017

Intravenous atrial natriuretic peptide (ANP) usually results in splanchnic vasoconstriction in humans or experimental animals that is accompanied by falls in blood pressure and/or cardiac output. To determine direct in vivo effects in the present study, ANP was infused (12 ng ⋅ kg−1⋅ min−1) directly into the mesenteric (iMA) and hepatic (iHA) arterial beds of anesthetized dogs, thereby minimizing changes in blood pressure. Over the first 2 min of iMA infusion, rate of change in mesenteric vascular resistance was 19.6 ± 5.4 mmHg ⋅ l−1⋅ min−1/min, reaching a maximum increase in resistance of 22 ± 4% compared with baseline after ∼10 min. There was no evidence of vasodilatation at any stage. The mesenteric response was similar whether ANP was infused iMA, iHA, or via the femoral vein (30 ng ⋅ kg−1⋅ min−1). In contrast, hepatic vasoconstrictor response to ANP infusion iHA or into the portal vein was only evident after ∼5 min, reaching a maximum increase in hepatic vascular resistance of 11 ± 6% after ∼15 min iHA infusion. When preinfused through the gut vasculature (iMA), ANP increased hepatic vascular resistance earlier and reached similar levels (14 ± 3%), despite a lower arterial concentration of ANP. It is proposed that a vasoconstrictor agent from the intestinal circulation contributed to ANP-induced splanchnic vasoconstriction.
Osmoregulatory control of renal sodium excretion after sodium loading in humans
Authors: Andersen Lars Juel , Norsk Peter , Johansen Lars Bo , Christensen Poul , Engstrøm Thomas , Bie Peter
Published: December 2017

The hypothesis that renal sodium handling is controlled by changes in plasma sodium concentration was tested in seated volunteers. A standard salt load (3.08 mmol/kg body wt over 120 min) was administered as 0.9% saline (Isot) or as 5% saline (Hypr) after 4 days of constant sodium intake of 75 (LoNa+) or 300 mmol/day (HiNa+). Hypr increased plasma sodium by ∼4 mmol/l but increased plasma volume and central venous pressure significantly less than Isot irrespective of diet. After LoNa+, Hypr induced a smaller increase in sodium excretion than Isot (48 ± 8 vs. 110 ± 17 μmol/min). However, after HiNa+the corresponding natriureses were identical (135 ± 33 vs. 139 ± 39 μmol/min), despite significant difference between the increases in central venous pressure. Decreases in plasma ANG II concentrations of 23–52% were inversely related to sodium excretion. Mean arterial pressure, plasma oxytocin and atrial natriuretic peptide concentrations, and urinary excretion rates of endothelin-1 and urodilatin remained unchanged. The results indicate that an increase in plasma sodium may contribute to the natriuresis of salt loading when salt intake is high, supporting the hypothesis that osmostimulated natriuresis is dependent on sodium balance in normal seated humans.
Dynamics of extracellular fluid volume changes during hyperproteinemia
Authors: Manning R. Davis
Published: December 2017

The dynamics of fluid volume distribution between the blood and interstitium during hyperproteinemia were studied in 12 anephric, conscious dogs during several states of hydration. After recovery from splenectomy and unilateral nephrectomy, plasma protein concentration was elevated to 8.4–8.7 g/dl by daily intravenous infusion of 330 ml of previously collected autologous plasma for 11 days. The remaining kidney was then removed, and the next day lactated Ringer solution equivalent to 10 or 20% of body weight was infused intravenously. By the end of the 25-h postinfusion period, Ringer infusion had increased circulating protein mass 20.9 ± 9.1% (mean ± SE) in the 10% group ( P< 0.05) and decreased it 10.5 ± 3.3% in the 20% group ( P < 0.05). The average increase in blood volume and arterial pressure during the postinfusion period was 27.4 ± 2.5 and 20.7 ± 3.7%, respectively, in the 10% group but only 17.8 ± 2.4 and 12 ± 1.6% in the 20% group (all changes significant compared with respective control). The relationship between blood volume and sodium space was similar to that found during normoproteinemia, such that elevations in sodium space of 40–50% increased blood volume but greater elevations in sodium space caused no further increases in blood volume. Overhydration during chronic hyperproteinemia causes hypervolemia and hypertension, but, in contrast to those in short-term studies, the increases in blood volume and arterial pressure are not greater than those achieved during normoproteinemia.
Association of fat cell size and paracrine growth factors in development of hyperplastic obesity
Authors: Marques Brenda G. , Hausman Dorothy B. , Martin Roy J.
Published: December 2017

Inguinal, epididymal, and retroperitoneal adipose tissue from lean and obese Zucker rats, 3–15 wk of age, was used to determine the association among adipocyte size distribution, the presence of paracrine growth factors in adipose tissue, and subsequent changes in adipocyte number. For each specific depot and time point, obese rats had a greater percentage of large adipocytes than did lean rats. A positive correlation ( P < 0.02) was found in obese rats between the percentage of inguinal and epididymal adipocytes in the 140- to 180-μm size range and the ability of conditioned medium prepared from these depots to stimulate cellular proliferation in a bioassay system utilizing preadipocytes from inguinal fat pads of normal rats. Proliferative activity of the conditioned medium from all depots in obese rats was positively correlated ( P < 0.01) to subsequent changes in fat cell number. The data presented here for the inguinal and epididymal depot of obese Zucker rats are consistent with the hypothesis that enlarged adipocytes secrete growth factors that induce preadipocyte proliferation.
Antagonism of ANG II type 1 receptors protects the endothelium during the early stages of renal hypertension in rats
Authors: Hoshino Jin , Nakamura Tetsuya , Kurashina Toshiaki , Saito Yuichiro , Sumino Hiroyuki , Ono Zenpei , Sakamoto Hironosuke , Kowase Keiko , Nagai Ryozo
Published: December 2017

The degree of involvement of the renin-angiotensin system in endothelial dysfunction was investigated by using a one-kidney, one-clip (1K,1C) model of renal hypertension. Male Wistar rats received 0.02% enalapril, 0.02% losartan, or tap water for 1 day before and for 48 h after the induction of renal artery stenosis or sham operation. The aorta of 1K,1C rats showed increased contraction and decreased relaxation responses produced by norepinephrine and acetylcholine, respectively, vs. control responses. Exposure to 10−5 mol/l N G-monomethyl-l-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in control rats than in the 1K,1C rats. The increased contraction and decreased relaxation responses to these agonists in the 1K,1C rats were normalized by enalapril or losartan. The addition of HOE-140 to the bath did not alter these normalized responses. Results suggest that angiotensin II causes endothelial dysfunction and reduces nitric oxide levels in 1K,1C rats. Such endothelial dysfunction enhanced the norepinephrine-induced contraction during the early-stage hypertension in 1K,1C rats.
Regulation of the sympathetic nerve discharge bursting pattern during heat stress
Authors: Kenney Michael J. , Claassen Dale E. , Bishop Michelle R. , Fels Richard J.
Published: December 2017

Frequency-domain analyses were used to determine the effect of heat stress on the relationships between the discharge bursts of sympathetic nerve pairs and sympathetic and phrenic nerve pairs in chloralose-anesthetized rats. Sympathetic nerve discharge (SND) was recorded from the renal, splanchnic, splenic, and lumbar nerves during increases in core body temperature (Tc) from 38 to 41.4 ± 0.3°C. The following observations were made: 1) hyperthermia transformed the cardiac-related bursting pattern of SND to a pattern that contained low-frequency, non-cardiac-related bursts, 2) the pattern transformation was uniform in regionally selective sympathetic nerves, 3) hyperthermia enhanced the frequency-domain coupling between SND and phrenic nerve bursts, and 4) low-frequency SND bursts recorded during hyperthermia contained significantly more activity than cardiac-related bursts. We conclude that acute heat stress profoundly affects the organization of neural circuits responsible for the frequency components in sympathetic nerve activity and that SND pattern transformation provides an important strategy for increasing the level of activity in sympathetic nerves during increased Tc.
Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons
Authors: Scrogin Karie E. , Johnson Alan Kim , Schmid Herbert A.
Published: December 2017

The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on SFO neurons. This study characterized the effects of serotonin on spontaneously firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% responded to serotonin (1–100 μM) with either an increase ( n = 15) or decrease ( n = 10) in spontaneous activity. Responses to serotonin were dose dependent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI; 1–10 μM) and could be blocked by the 5-HT2A/2C-receptor antagonist LY-53,857 (10 μM). LY-53,857 unmasked inhibitory responses to serotonin in 56% of serotonin-excited cells tested. Serotonin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hydroxy-2(di- n-propylamino)tetralin (8-OH-DPAT; 1–10 μM; n = 7). The data indicate that SFO neurons are responsive to serotonin via postsynaptic activation of multiple receptor subtypes. The results suggest that excitatory responses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that inhibitory responses may be mediated by 5-HT1A receptors. In addition, similar percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG II in the SFO remains unclear.
Leptin acts in the rat hypothalamic paraventricular nucleus to induce gastric mucosal damage
Authors: Smith Pauline M. , Mollaret Veronique , Ferguson Alastair V.
Published: December 2017

Leptin is produced and secreted by adipocytes to regulate body weight homeostasis. Leptin acts centrally to reduce weight by decreasing food intake and increasing energy expenditure. The paraventricular nucleus (PVN) is a central nervous system structure suggested as a site at which leptin acts to exert its central effects. Leptin microinjection (10−6 M, 0.5 μl) into the PVN of urethan-anesthetized male Sprague-Dawley rats (150–300 g) resulted in significant gastric damage (mean score = 1.75, n = 16). Damage scores were significantly different than those observed after saline microinjection into the PVN (mean score = 0.00, n = 5, P < 0.05), or leptin microinjection into non-PVN sites (mean score = 0.33, n = 6, P < 0.05). There were no changes in blood pressure (mean area under curve = 401.9 ± 224.2 mmHg * s, n = 11, P > 0.05) or heart rate (mean area under curve = 40.9 ± 25.9 beats, n= 10, P > 0.05) in response to leptin microinjection into PVN. These results suggest that leptin acts on a functionally specific population of PVN neurons involved in the control of gastrointestinal function.
Cold exposure regulates the norepinephrine uptake transporter in rat brown adipose tissue
Authors: King Victoria L. , Dwoskin Linda P. , Cassis Lisa A.
Published: December 2017

The neuronal uptake of norepinephrine (NE) in sympathetically innervated tissues is mediated by a high-affinity NE uptake transporter (NET). Rat interscapular brown adipose tissue (ISBAT) is densely innervated by the sympathetic nervous system for the control of cold- and diet-induced thermogenesis. To determine if cold exposure regulates the NET, kinetic parameters for [3H]NE uptake and [3H]nisoxetine (Nis) binding were determined in ISBAT from 7-day cold-exposed (CE) and control rats. Uptake of [3H]NE in ISBAT slices was of high affinity (1.6 μM). After 7 days of cold exposure the affinity for [3H]NE uptake was not altered; however, the uptake capacity was decreased (38%) in ISBAT slices from CE rats. Kinetic parameters for [3H]Nis binding demonstrated a single high-affinity site in ISBAT from CE and control rats with similar affinity. The density of [3H]Nis sites in ISBAT was decreased (38%) following cold exposure. A time course (2 h-7 days) for cold exposure demonstrated downregulation of [3H]Nis binding density by day 3, which remained through day 7. The affinity for [3H]Nis binding was transiently decreased at 2 h of cold exposure. Similarly, ISBAT NE content was decreased at 2 h of cold exposure. Pair feeding CE rats to food intake of controls normalized plasma NE content; however, [3H]Nis binding density in ISBAT remained decreased in pair-fed rats. These results demonstrate that the ISBAT NET is downregulated following cold exposure. Reductions in ISBAT NE content precede alterations in NET density; however, plasma NE content is not related to regulation of the NET.
Potassium fluxes in contracting human skeletal muscle and red blood cells
Authors: Juel C. , Hellsten Y. , Saltin B. , Bangsbo J.
Published: December 2017

The present study examined K+ fluxes in red blood cells and muscle during muscle contractions. Seven subjects performed two-legged submaximal knee-extensor exercise for 30 min. After 10 min of leg exercise ( L1), intense arm exercise was also performed for 10 min ( L2+A). Plasma epinephrine and norepinephrine concentrations were higher ( P < 0.05) in L2+A compared with L1. Arterial plasma K+ at the end of L2+A was higher than in L1 (5.6 vs. 4.4 mM, P < 0.05) and returned to the L1 level on cessation of arm exercise. A net K+ release of 0.16 mmol/min from the active legs during L1 was turned to a net K+ uptake of 0.79 mmol/min during L2+A. Both arterial and venous red blood cell K+-to-hemoglobin ratios were constant during exercise. The present data suggest that contracting muscle can take up K+ probably by a combination of K+ and hormone activation of the Na+-K+pump. Furthermore, changes in red blood cell K+ concentrations during muscle activity appear to be due to water movements and not transmembrane fluxes of K+.