bluuebunny/crossref_metadata_2025 huggingface dataset:
Vigilance states, EEG spectra, and cortical temperature in the guinea pig
Authors: Tobler I. , Franken P. , Jaggi K.
Published: December 2017

Vigilance states, electroencephalogram (EEG) power spectra (0.25-25.0 Hz), and cortical temperature (TCRT) were obtained in nine guinea pigs for 24 h in a 12:12-h light-dark (LD 12:12) schedule. Sleep was markedly polyphasic and fragmented and amounted to 32% of recording time, which is a low value compared with sleep in other rodents. There was 6.8% more sleep in the light period than in the dark period. EEG power density in non-rapid eye movement (NREM) sleep showed no significant temporal trend within the light or the dark period. The homeostatic aspects of sleep regulation, as proposed in the two-process model, can account for the slow-wave activity (SWA) pattern also in the guinea pig: The small 24-h amplitude of the sleep-wakefulness pattern resulted in a small, 12% decline of SWA within the light period. In contrast to more distinctly nocturnal rodents, SWA in the dark period was not higher than in the light period. TCRT showed no difference between the light and the dark period. TCRT in REM sleep and waking was higher than TCRT in NREM sleep. TCRT increased after the transition from NREM sleep to either REM sleep or waking, and decreased in the last minute before the transition and after the transition from waking to NREM sleep. Motor activity measured in six animals for 11 days in constant darkness showed no apparent rhythm in three animals and a significant circadian rhythm in three others. Our data support the notion that guinea pigs exhibit only a weak circadian rest-activity rhythm.
Suprachiasmatic nucleus lesion increases corticosterone secretion
Authors: Buijs R. M. , Kalsbeek A. , van der Woude T. P. , van Heerikhuize J. J. , Shinn S.
Published: December 2017

The diurnal rhythm of corticosteroid secretion is controlled by the suprachiasmatic nucleus (SCN). In rats, plasma corticosteroid levels rise just before the onset of the activity period during the dark phase. Our previous results indicated that vasopressin as a neurotransmitter from the SCN inhibited corticosteroid secretion in the area of the paraventricular/dorsomedial nucleus of the hypothalamus. We hypothesized that during the day the SCN may serve as an inhibitory system for corticosteroid secretion. To investigate this possibility, intact and SCN-lesioned animals were exposed to mild stress in the morning and evening and their plasma corticosteroid levels were monitored. The results indicate that SCN-lesioned animals have higher morning corticosteroid levels and respond both in the morning and evening with higher corticosteroid levels after stress than do intact control animals. We conclude, therefore, that these results indicate an inhibitory role of the SCN on corticosteroid secretion. The apparent discrepancy with the reported stimulatory role of the SCN on adrenocorticotropic hormone secretion is discussed.
Skeletal muscle glucose metabolism in obesity-prone and obesity-resistant rats
Authors: Pagliassotti M. J. , Shahrokhi K. A. , Hill J. O.
Published: December 2017

Ad libitum access to a high-fat (HF) diet produces a wide range of weight gain in rats. Rats most susceptible to weight gain on such a diet (obesity prone; OP) are more insulin resistant after 4-5 wk of diet exposure than are those most resistant (obesity resistant; OR) to weight gain. To investigate whether skeletal muscle glucose metabolism contributes to insulin resistance in this model, insulin-stimulated glucose metabolism was assessed in the perfused hindquarter of rats exposed to either a low-fat (LF, n = 6) or HF diet for 5 wk. Delineation of OP (n = 6) and OR (n = 6) rats was based on body weight gain. OP rats gained 60% more body weight while eating only 10% more energy than OR rats. Single-pass perfusions were carried out for 2 h in the presence of glucose, insulin, and [U-14C]glucose. Insulin-stimulated glucose uptake (mumol.100 g-1.min-1) was 14.2 +/- 0.9 in LF, 11.1 +/- 0.8 in OR, and 6.2 +/- 0.6 in OP. Glucose oxidation (mumol.100 g-1.min-1) was 1.7 +/- 0.3 and 1.2 +/- 0.3 in LF and OR, respectively, but was 0.2 +/- 0.1 in OP. Net glycogen synthesis was significantly reduced in OP compared with OR and LF despite similar glycogen synthase I activity. Muscle triglyceride concentration was not significantly different in OR and OP rats. These results demonstrate significant defects in skeletal muscle glucose uptake and disposal in rats most susceptible to HF diet-induced obesity. Clearly, the heterogeneous response to a HF diet involves not only body weight gain but also skeletal muscle fuel metabolism.
Endogenous cholecystokinin in the control of gastric emptying of liquid nutrient loads in rhesus monkeys
Authors: Moran T. H. , Ameglio P. J. , Schwartz G. J. , Peyton H. J. , McHugh P. R.
Published: December 2017

A role for the brain/gut peptide cholecystokinin (CCK) in the control of gastric emptying has been proposed. In the present studies, we have used a potent type A CCK-receptor antagonist (devazepide) to examine the quantitative contribution of endogenously released CCK in the control of liquid gastric emptying of 100 ml lipid, protein, and carbohydrate test loads in rhesus monkeys. Emptying was studied in conscious monkeys equipped with chronic indwelling gastric cannulas. Prior intragastric administration of devazepide (1.0-320 micrograms/kg) differentially affected the 10-min emptying of glucose (0.125/ml), peptone (4.5%), and Intralipid (4.5%). Glucose emptying was not affected by any dose of the CCK antagonist. The emptying of peptone was accelerated by doses of 10 micrograms/kg or higher. This effect, however, was only partial and plateaued at a dose of 100 micrograms/kg. The gastric emptying of Intralipid was accelerated at a dose of 32 micrograms/kg, and the inhibitory effect of the Intralipid was completely eliminated at a dose of 320 micrograms/kg. At this dose of devazepide, the Intralipid test meal emptied from the stomach at the same rate as physiological saline. These data demonstrate that in rhesus monkeys endogenously released CCK 1) does not play a role in the control of glucose emptying, 2) is a partial mediator of the inhibitory action of peptone on gastric emptying, and 3) is the primary inhibitory mediator in the control of the gastric emptying of Intralipid.
Effects of long-term restricted feeding on motor activity rhythm in the rat
Authors: Cambras T. , Vilaplana J. , Diez-Noguera A.
Published: December 2017

The motor activity circadian rhythm of the rat is driven by at least two different pacemakers, one entrained by light-dark cycles and the other by periodic food access. The interaction between these two pacemakers generates the overt rhythm in many variables in the rat. In this paper we study the effects of restricted feeding (RF) for > 300 days on the motor activity of two groups of eight rats each (4 males and 4 females) that were kept under different light patterns. The first group was kept under dim red light, and the second group was kept initially for 70 days under bright light and afterward under dim red light. Rats had access to food for only 2 h/day. Results show that strong alterations in the motor activity pattern, such as relative coordination, bouncing, and several cases of entrainment, are shown in the first group. When these animals return to ad libitum feeding conditions the presence of the food component is clear, in some cases for > 20 days. In contrast, the rats that were previously subjected to bright light did not entrain to RF. In this group, there was a masking effect when lights were on, but a free-running component appeared when lights were off. The endogenous period (tau) of this component was not modified during the course of the experiment. After RF these rats showed a longer tau than the former group.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of V1 receptors in the action of vasopressin on the baroreflex control of heart rate
Authors: Luk J. , Ajaelo I. , Wong V. , Wong J. , Chang D. , Chou L. , Reid I. A.
Published: December 2017

Arginine vasopressin (AVP) elicits a larger decrease in heart rate for a given increase in arterial pressure than do other vasoconstrictors, but there is disagreement as to whether this results from an increase in baroreflex gain or a resetting of the baroreflex to a lower blood pressure. It is also unclear which type of vasopressin receptor mediates the action of vasopressin on the baroreflex. In the present study, the effects of vasopressin, selective vasopressin V1 and V2 receptor agonists, oxytocin, and a vasopressin V1 receptor antagonist on the baroreflex control of heart rate were investigated in conscious, chronically prepared rabbits. Baroreflex curves were generated with intravenous infusions of phenylephrine and nitroprusside and analyzed using a four-parameter logistic model. Intravenous infusion of vasopressin at 5 ng.kg-1.min-1 increased mean arterial pressure by 9 mmHg and decreased heart rate by 31 beats/min. The arterial pressure at the midrange of the baroreflex curve (BP50) decreased from 75.9 +/- 4.8 to 57.6 +/- 1.7 mmHg (P < 0.01), indicating a shift of the baroreflex curve to a lower pressure, but the gain did not change significantly. The actions of vasopressin on blood pressure, heart rate, and BP50 were completely blocked by pretreatment with d(CH2)5[Tyr(Me)2]AVP, a selective V1 receptor antagonist. Infusion of [Phe2,Ile3,Orn8]AVP, a selective V1 receptor agonist, produced cardiovascular effects similar to those of vasopressin and decreased the BP50 of the baroreflex from 73.0 +/- 2.2 to 63.8 +/- 2.2 mmHg (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin-mediated glycogen synthase activity in muscle of spontaneously insulin-resistant and diabetic rhesus monkeys
Authors: Ortmeyer H. K. , Bodkin N. L. , Hansen B. C.
Published: December 2017

Altered insulin action on glycogen synthase activity has been well recognized in non-insulin-dependent diabetes, and some prior evidence has suggested this alteration may be one of the earliest disturbances preceding the development of diabetes. The present study, using the spontaneously insulin-resistant and diabetic rhesus monkey, examined insulin's effect on glycogen synthase at the earliest point of identification of developing diabetes. The normal monkeys (n = 11) had a greater insulin-mediated change in glycogen synthase-independent activity compared with the hyperinsulinemic (n = 8) (P < 0.05) and diabetic (n = 8) (P < 0.01) monkeys. Compared with normal monkeys, the diabetic monkeys had lower basal and insulin-stimulated total glycogen synthase activity (P < 0.05). Monkeys with normal beta-cell responsiveness to intravenous glucose had greater insulin-mediated change in glycogen synthase fractional velocity compared with those with exaggerated (P < 0.01) or absent beta-cell responses to glucose (P < 0.05). We conclude that an alteration in insulin action on glycogen synthase is present as early as beta-cell hyperresponsiveness, one of the earliest detected abnormalities in the progression toward diabetes.
Endothelium-derived relaxing factor responses in Doca-salt hypertensive rats
Authors: Kirchner K. A. , Scanlon P. H. , Dzielak D. J. , Hester R. L.
Published: December 2017

This study examined the contribution of endothelium-derived relaxing factor (EDRF) to the susceptibility of uninephrectomized rats to deoxycorticosterone acetate (DOCA)-salt hypertension. N omega-nitro-L-arginine, a probe for EDRF, produced smaller increases (P < 0.001) in mean arterial pressures in anesthetized hypertensive DOCA-salt rats than in sham rats. Acute L-arginine administration (300 mg/kg body wt i.v.) failed to reduce pressure in anesthetized DOCA-salt rats. Chronic oral and intraperitoneal L-arginine did not lower pressure in conscious DOCA-salt rats with established hypertension, nor did it prevent hypertension when begun in prehypertensive DOCA-salt rats. Preconstricted aortic rings from DOCA-salt rats had attenuated relaxation to acetylcholine compared with sham rats. Rings L-arginine-treated DOCA-salt rats had responses similar to DOCA-salt rats. Relaxation to nitroprusside was not different between any rat group. Thus EDRF is attenuated in DOCA-salt hypertension. However, unlike several other hypertensive models, the blunted EDRF response cannot be overcome by provision of L-arginine. These data suggest synthesis or release of EDRF may be noncompetitively inhibited in DOCA-salt hypertension.
Intestinal lymphatic pressure increases during intravenous infusions in awake sheep
Authors: Drake R. E. , Anwar Z. , Kee S. , Gabel J. C.
Published: December 2017

Intravenous fluid infusions cause increased venous pressure and increased lymph flow throughout the body. Together the increased lymph flow and increased venous pressure (the outflow pressure to the lymphatic system) should increase the pressure within the postnodal intestinal lymphatics. To test this, we measured the pressure in postnodal intestinal lymphatics and the neck vein pressure in five awake sheep. At baseline, the neck vein pressure was 1.2 +/- 1.5 (SD) cmH2O and the lymphatic pressure was 12.5 +/- 1.7 cmH2O. When we infused Ringer solution intravenously (10% body weight in approximately 50 min), the neck vein pressure increased to 17.3 +/- 0.9 cmH2O and the lymphatic pressure increased to 24.6 +/- 3.8 cmH2O (both P < 0.05). In two additional sheep, the thoracic duct lymph flow rate increased from 0.8 +/- 0.4 ml/min at baseline to 5.5 +/- 2.0 ml/min during the infusions. Our results show that postnodal intestinal lymphatic pressure may increase substantially during intravenous fluid infusions. This is important because increases in postnodal lymphatic pressure may slow lymph flow from the intestine.
A quantitative method for classification of EEG in the fetal baboon
Authors: Myers M. M. , Stark R. I. , Fifer W. P. , Grieve P. G. , Haiken J. , Leung K. , Schulze K. F.
Published: December 2017

Electroencephalographic (EEG) activity is used as a primary indicator of sleep states in adults and infants of many species and in the ovine fetus. We recently reported that the baboon fetus exhibits visually discernable patterns of EEG activity. One pattern of activity, characterized by the intermittent presence of repetitive bursts of high-voltage EEG, is indistinguishable from trace alternant (TA). TA is a distinctive pattern of EEG activity found only during early stages of development in primates. TA is the predominant pattern of EEG activity during quiet sleep in human infants < 2 mo of age. The focus of this study was to derive quantitative parameters that would discriminate TA from other activity and then to develop a method for automated categorization of EEG patterns. Results demonstrate that several parameters derived from frequency-domain analyses are related to visually coded EEG states. Among these parameters, high-frequency power (12-24 Hz) and spectral-edge frequency are good discriminators of EEG patterns. This paper describes a new parameter, EEG ratio, computed as spectral power in the rectified EEG within a band that corresponds to the frequency of bursts of activity during TA (0.03-0.20 Hz) divided by power in the 12- to 24-Hz band. This new composite parameter of EEG activity provides a markedly better correlate of visually coded EEG than any of the individual parameters tested. Using cluster analysis, we devised a method for objective minute-by-minute dichotomization of EEG ratio. The method produces results that agree with visual coding of EEG activity 87.1% of the time.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of a central CRF antagonist on cardiovascular and thermoregulatory responses induced by stress or IL-1 beta
Authors: Nakamori T. , Morimoto A. , Murakami N.
Published: December 2017

We investigated the role of central corticotropin-releasing factor (CRF) in the development of cardiovascular and thermal responses induced by stress or by interleukin-1 beta (IL-1 beta) in free-moving rats. Intracerebroventricular (icv) injection of alpha-helical CRF9-41 (10 micrograms), a CRF receptor antagonist, significantly attenuated hypertension, tachycardia, and a rise in body temperature induced by cage-switch stress, a mild stress. However, icv injection of alpha-helical CRF9-41 (10 micrograms) had no effect on hypertension, tachycardia, or fever induced by intraperitoneal (ip) injection of IL-1 beta (2 micrograms/kg) or icv prostaglandin E2 (PGE2, 100 ng). In contrast, icv injection of alpha-helical CRF9-41 (10 micrograms) significantly attenuated hypertension, tachycardia, or fever induced by icv injection of IL-1 beta (20 ng). The present results suggest that central CRF has an important role in the development of the cage-switch stress-induced responses, but it does not seem to contribute to the hypertension, tachycardia, and fever induced by ip IL-1 beta or by central PGE2. However, it is possible that when IL-1 beta directly acts on the central nervous system, some of its actions are mediated by central CRF.
Microcalorimetric measurement of reversible metabolic suppression induced by anoxia in isolated hepatocytes
Authors: Buck L. T. , Hochachka P. W. , Schon A. , Gnaiger E.
Published: December 2017

The metabolic suppression due to anoxia in hepatocytes from the anoxia-tolerant turtle Chrysemys picta bellii was measured directly using microcalorimetric techniques. The normoxic heat flux from hepatocytes in suspension (25 degrees C) was 1.08 +/- 0.08 mW/g cells and decreased by 76% to 0.26 +/- 0.03 mW/g cells in response to anoxic incubation. After an acute decrease in temperature (to 10 degrees C) anoxic heat flux dropped by 96% relative to the normoxic control at 25 degrees C. The relative decrease in heat flux at both temperatures was similar, 76% at 25 degrees C and 68% at 10 degrees C. From the caloric equivalent of glycogen fermentation to lactate the heat flux from lactate production was calculated to be -93 microW/g cells (25 degrees C), and this accounted for 36% of the anoxic heat flux. When the enthalpy change associated with the release of free glucose (from glycogen breakdown) is considered, an additional 6% of the anoxic heat flux can be accounted for. Therefore, a portion of the anoxic heat flux is unaccounted for (58%), resulting in an “exothermic gap.” This differs from the normoxically incubated hepatocytes where the indirect calorimetric measurement of heat flux (hepatocyte O2 consumption) could fully account for the calorimetrically measured heat flux. When normoxic hepatocytes were inhibited with cyanide, a rapid suppression in heat flux was observed. Because rapid reequilibration to a lower, cyanide-induced steady state occurred in < 15 min, it is also assumed that there is no short-term Pasteur effect in this tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Central cardiovascular effects of joining peptide in genetically hypertensive rats
Authors: Hamakubo T. , Yoshida M. , Nakajima K. , Watanabe T. X. , Mosqueda-Garcia R. , Inagami T.
Published: December 2017

Joining peptide (JP) is one of the major products of proopiomelanocortin (POMC). The biological function of this peptide has not been clarified despite its relative abundance in the pituitary and the hypothalamus. Recently we demonstrated that JP, which was isolated from bovine posterior pituitary, possesses Na pump inhibitor activity. The purpose of this study is to explore the physiological relevance of JP in cardiovascular regulation. For these investigations, we used the synthetic peptides bovine JP (bJP) and COOH-terminally amidated rat JP (rJP), since JP is known to have sequence variability among species. Intracisternal administration of both bJP and rJP in urethan-anesthetized rats evoked similar hypertensive and tachycardia effects. The effects of both peptides were markedly greater in the spontaneously hypertensive rats (SHR) compared with the normotensive Wistar Kyoto rats (WKY). Intravenous bolus injections of rJP at the same doses were without effect. Autoradiography, using 125I-labeled [0Tyr]-rJP as a ligand, revealed specific binding sites for rJP in the dorsal medulla in areas corresponding to the nucleus tractus solitarii (NTS) (extending from approximately 0.4 mm caudal to 1.8 mm rostral to the obex). Microinjections of rJP into the caudal part of the NTS of anesthetized SHR produced dose-related pressor and tachycardic responses. The pressor and tachycardic responses were also observed at the rostral part of the NTS, whereas the injections into the intermediate part of the NTS evoked depressor and bradycardic responses in SHR. These results suggest that at doses tested, the site of JP action resides in the central nervous system, and that JP is a potent neuropeptide in medullary sites known to be pivotal in central cardiovascular regulation. The effect of JP is especially prominent in the genetically hypertensive rat.
Effect of somatostatin on circadian rhythms of firing and 2-deoxyglucose uptake in rat suprachiasmatic slices
Authors: Hamada T. , Shibata S. , Tsuneyoshi A. , Tominaga K. , Watanabe S.
Published: December 2017

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus appears to act as a circadian clock. The SCN vasoactive intestinal polypeptide-like immunoreactive neurons, which may act to mediate photic information in the SCN, receive input from neurons immunoreactive for somatostatin (SST). Therefore we investigated the role of SST as a transmitter for entrainment by analyzing the phase-resetting effect of SST on the circadian rhythm of SCN firing activity. Perfusion of SST increased 2-deoxyglucose uptake at circadian time (CT) 18, but not at CT6. A 1-h or 15-min treatment with SST produced phase delays when it was administered at CT13-14 and phase advances at CT22-23. Thus SST-induced phase changes are similar to those for light pulses to animals under constant darkness. The present findings suggest that SST is a transmitter for mediating information of entrainment to circadian clocks within the SCN.
Cerebral metabolism and electrocortical activity in the chronically hyperglycemic fetal lamb
Authors: Rosenkrantz T. S. , Knox I. , Zalneraitis E. L. , Raye J. R. , Porte P. J. , Cramer R. , Smoloski R. , Phillipps A. F.
Published: December 2017

Previous studies in the fetal lamb have demonstrated that hyperglycemia stimulates the fetal metabolic rate. The present study examined the effects of chronic fetal hyperglycemia on fetal cerebral metabolic rate and electrocortical activity. Nine chronically instrumented fetal lambs had measurements of cerebral blood flow and cerebral uptake/excretion of oxygen, glucose, lactate, and beta-hydroxybutyrate taken before and during a 48-h fetal glucose infusion. Electrocortical activity was also recorded. The fetal arterial glucose concentration was 19.8 +/- 2.0 mg/dl before glucose infusion and 48 +/- 4.5 to 54.6 +/- 6.6 mg/dl during the infusion period. Cerebral blood flow and cerebral glucose and oxygen uptake increased by 219, 209, and 171%, respectively, by the end of the infusion period. There was a linear relationship between the fetal arterial glucose concentration and cerebral blood flow and cerebral glucose and oxygen uptakes. The electroencephalogram showed significant slowing with increases in the cerebral metabolic rate. These findings suggest that fetal hyperglycemia is associated with significant metabolic stimulation of the brain.
Role of olfaction in starch and oil preference
Authors: Ramirez I.
Published: December 2017

Two different techniques were used to assess the role of olfaction in the preference rats show for dilute nutrient suspensions and solutions. Removal of the olfactory bulbs reduced but did not abolish preference for 1% starch and oil emulsions. Removal of the olfactory bulbs also reduced preference for sucrose, Polycose, and saccharin. In another experiment, rats were rendered anosmic with intranasal zinc sulfate. The degree of anosmia was evaluated by measuring preference for an aqueous solution of citral and vanillin. Rats whose avoidance of citral plus vanillin had been abolished by zinc sulfate continued to prefer a 1% starch suspension over vehicle, although starch preference was significantly reduced. It is concluded that starch and oil preference is mediated by both olfactory and nonolfactory cues.
Hyperthermia protects mice against the lethal effects of endotoxin
Authors: Hotchkiss R. , Nunnally I. , Lindquist S. , Taulien J. , Perdrizet G. , Karl I.
Published: December 2017

Recently, investigators have reported that heat shock proteins (HSPs) can protect isolated cells from cytotoxicity induced by two important mediators of sepsis: interleukin-1 and tumor necrosis factor. The present study was undertaken to examine the hypothesis that transient whole body hyperthermia could decrease mortality from subsequent challenge with gram-negative endotoxin. We demonstrate that heat pretreatments improved long-term survival fivefold in a mouse endotoxin model and this was correlated with the production of HSPs. There was a marked difference in individual organ expression of the inducible 72-kDa heat shock protein (HSP72). Heat treatments caused significant HSP72 formation in lung, liver, kidney, and small intestine, but much lesser formation in heart, brain, and abdominal wall muscle. Additional experiments demonstrated that the protective effect of hyperthermic treatments against an endotoxin challenge occurred early, i.e., 1 and 2 h after heating, was maximal at 12 h, and had significantly diminished by 48 h. The formation and decay of HSP72 demonstrated a time course that paralleled the survival curve from endotoxin challenge, thus suggesting a possible role for HSP72 in the protective effect. Surprisingly, and in contrast to studies reported in incubated cells, endotoxin alone did not cause significant formation of HSP72 in vivo.
ANF-C-receptor-mediated inhibition of aortic smooth muscle cell proliferation and thymidine kinase activity
Authors: Cahill P. A. , Hassid A.
Published: December 2017

We have investigated the inhibition of DNA synthesis and cell proliferation by rat atrial natriuretic factor [rANF-(99-126)] and several synthetic peptides that bind selectively to the ANF-C-type clearance receptors in subcultured aortic smooth muscle cells. These peptides decreased serum-induced 1) [3H]thymidine incorporation, 2) cell proliferation, and 3) thymidine kinase activity without altering basal or elevated cAMP or cGMP levels. In contrast, another ANF-C-receptor-binding peptide, des[Gln116,Ser117,Gly118,Leu119,Gly120] rANF-(102-121)-NH2 (cANF), failed to decrease serum-induced mitogenesis, yet 100 nM cANF reversed the inhibition of DNA synthesis and cell proliferation and the decrease of thymidine kinase activity elicited by other C receptor-binding peptides, including rANF-(99-126), rANF-(103-125), and porcine C-type natriuretic peptide [pCNP-(1-22)]. Delayed addition experiments indicated that atrial peptides influence a relatively late event (or events) during the G1 phase of the cell cycle. The inhibition of DNA synthesis by C-receptor-binding atrial peptides appeared to be selective for aortic smooth muscle cells, inasmuch as a potent inhibitory agonist peptide, Cys116-rANF-(102-116), was without significant influence on the incorporation of thymidine in cultured rat mesangial cells or bovine pulmonary artery endothelial cells. These results indicate that atrial natriuretic peptide analogues decrease vascular smooth muscle cell mitogenesis and proliferation by a cyclic nucleotide-independent mechanism involving the C-type receptor. Moreover the inhibition of DNA synthesis by rANF-(99-126) and the neuropeptide pCNP-(1-22) appears to be mediated by the ANF-C-type receptor and is associated with inhibition of thymidine kinase activity.
Hypothermia to endotoxin involves the cytokine tumor necrosis factor and the neuropeptide vasopressin in rats
Authors: Derijk R. H. , Berkenbosch F.
Published: December 2017

Previously, we have reported that intravenous administration of bacterial endotoxin (lipopolysaccharide, LPS) in rats kept at a subthermoneutral ambient temperature of 24 degrees C results in a fall in colonic temperature that involved the release of antipyretic products by peripheral macrophages. Here, we demonstrate that treatment of rats with a biologically active antiserum to tumor necrosis factor (TNF) markedly attenuates the hypothermia in response to administration of LPS (0.5 mg/kg). Moreover, this hypothermia was prevented by central injection of a selective antagonist of V1 vasopressin receptors, dPTyr(Me) arginine vasopressin (AVP; 2 micrograms icv). AVP is thought to act as an antipyretic in the ventral septal area (VSA) of the brain. Because the AVP content of this area has been shown to be eliminated after long-term castration, we have tested the hypothesis that castration would attenuate the hypothermia in response to administration of LPS. Castrated rats displayed a markedly less hypothermic response than age-matched controls in response to administration of LPS. We conclude that hypothermia in response to intravenous injection of LPS involves the release of TNF from peripheral macrophages. Moreover, our results are consistent with the possibility that androgen-dependent vasopressinergic neurons in the VSA are mediating the hypothermia in response to intravenous administration of LPS.
Increase of human platelet serotonin uptake by atypical histamine receptors
Authors: Launay J. M. , Bondoux D. , Oset-Gasque M. J. , Emami S. , Mutel V. , Haimart M. , Gespach C.
Published: December 2017

Histamine and the guanosine 3',5'-cyclic monophosphate (cGMP)-inducing agent sodium nitroprusside both increased serotonin (5-HT) uptake and cGMP levels in isolated human platelets in vitro. Histaminergic stimulation was observed at concentrations ranging from 10 nM to 0.25 microM [mean effective concentration (EC50) = 0.1 microM histamine]. The inhibition produced by the H2-receptor antagonists tiotidine, metiamide, and cimetidine was 10-10(5) times more potent on histamine receptors regulating 5-HT uptake and cGMP generation in human platelets than on the histaminergic receptors H1, HIC, H2, and H3 in other tissues. The in vitro histamine-induced 5-HT uptake was prevented by preincubation of isolated human platelets in the presence of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine or the cGMP-lowering agent LY-83583. Histamine was ineffective in stimulating cAMP generation in human platelets and did not interact with effector sites known to downregulate 5-HT uptake, including imipramine, gamma-aminobutyric acid A, peripheral type benzodiazepine-binding sites, and V1a vasopressin receptors inducing human platelet shape change and aggregation. These atypical human platelet histaminergic receptors differ from the previously classified histamine receptors by their apparent high affinity to histamine H2-receptor antagonists and their apparent link with the soluble, nitric oxide-dependent guanylate cyclase. These findings suggest that human platelets express a new subtype H2h of histamine receptors.
A gradient-layer calorimeter for measurement of energy expenditure of infants
Authors: Meis S. J. , Dove E. L. , Bell E. F. , Thompson C. M. , Glatzl-Hawlik M. A. , Gants A. L. , Kim W. K.
Published: December 2017

We have developed and validated a gradient-layer calorimeter for direct measurement of energy expenditure of preterm infants. Infant calorimeters must be operated and tested differently from adult calorimeters, because the calorimeter must be warmed during operation to limit heat loss from the infant, the calorimeter wall temperature (which is selected on the basis of the infant's maturity) must be precisely controlled, and energy expenditure (heat output) is typically < 10 W. We calibrated our calorimeter by varying the heat produced by a dry source (manikin or light bulb) with airflow (n = 42) and without airflow (n = 8) at various water jacket temperatures (n = 7) and by a wet source (combustion of ethyl alcohol) with airflow (n = 9). With no air moving, qc = 0.740 Vc + 0.029 Twj-0.697, where qc (W) is the estimated output of the heat source measured by the calorimeter, Vc (mV) is the gradient-layer voltage of the calorimeter, and Twj (degree C) is the temperature of the water jacket surrounding the walls of the device. From this equation and enthalpy calculations, the slope and intercept of the regression line relating the estimated heat production to the actual heat produced from alcohol combustion are 1.029 +/- 0.046 and -0.549 +/- 0.484 (SE), respectively. The slope is not significantly different from unity, and the intercept is not significantly different from zero. Thus we can accurately estimate the energy expenditure of preterm infants from the equations describing our calorimeter, and we can accurately resolve the total heat output into a dry (nonevaporative) component and a wet (evaporative) component.
Influences of renal nerves and pregnancy on renin secretion in sheep
Authors: Fan L. , Archambault D. , Chavez S. , Aljabari A. W. , Quillen E. W.
Published: December 2017

To investigate the role of the renal nerves in the control of renin secretion during pregnancy, we prepared sheep with one denervated kidney, bilateral renal vein catheters, and an inflatable aortic occluder. The renin secretory responses to step reductions of renal perfusion pressure (RPP) of the innervated and denervated kidneys were compared in eight nonpregnant and nine pregnant (115-130 days gestation) sheep in a normal conscious state. Nonpregnant sheep had average basal levels of mean arterial pressure (MAP) of 91 +/- 3 mmHg, plasma renin activities (PRA) of 2.3 +/- 0.4 ng ANG I.ml-1.3 h-1, and plasma angiotensin (ANG) concentrations of 8.4 +/- 1.1 pg/ml. Pregnant sheep had reduced levels (P < 0.01) of MAP (76 +/- 3 mmHg) but elevated levels of PRA (3.8 +/- 0.4 ng ANG I.ml-1.h 3-1; P < 0.5) and ANG II (12.0 +/- 1.6 pg/ml; P = 0.08). Four successively reduced levels of RPP were observed for 15 min each in both groups of sheep. In both groups, RPP was reduced to a final level of 51 +/- 2 mmHg. The renal venous-arterial difference of PRA (v-aPRA) from the innervated kidneys was increased as RPP was reduced. However, there was little response of v-aPRA to RPP in denervated kidneys. In nonpregnant sheep, the relationship between RPP and renin secretion rate was characterized by an initially slow phase, over which small reductions of RPP resulted in small increases in renin secretion. As RPP fell, this relationship became progressively steeper in nonpregnant ewes.(ABSTRACT TRUNCATED AT 250 WORDS)
Renin and vasopressin responses to graded reductions in atrial pressure in conscious dogs
Authors: O'Donnell C. P. , Thompson C. J. , Keil L. C. , Thrasher T. N.
Published: December 2017

Hypovolemia activates reflexes that stimulate secretion of renin and arginine vasopressin (AVP). A large body of evidence, obtained mainly in anesthetized preparations, supports the hypothesis that unloading cardiac receptors stimulates increases in plasma AVP and renin activity (PRA). We have observed significant increases in PRA before any change in either mean arterial pressure (MAP) or pulse pressure in conscious dogs undergoing continuous hemorrhage; however, plasma AVP did not change until there was a significant fall in MAP. These results are compatible with the hypothesis that cardiac receptors cause reflex stimulation of renin but not AVP secretion. The aim of the present study was to test the hypothesis that a decrease in atrial pressure alone is sufficient to stimulate an increase in plasma AVP and PRA. Graded thoracic inferior vena caval constriction (TIVCC) was used to reduce atrial pressure in four steps without altering MAP in conscious dogs. In a fifth step, TIVCC was increased to cause a fall in MAP. A reduction in left atrial pressure (LAP) of 4.2 +/- 0.9 mmHg was accompanied by a significant (P < 0.05) increase in PRA from a control value of 0.4 +/- 0.1 ng angiotensin I (ANG I).ml-1.3 h-1 to 1.1 +/- 0.2 ng ANG I.ml-1.3 h-1 but no change in plasma AVP (from 1.0 +/- 0.1 to 1.2 +/- 0.2 pg/ml) or MAP (from 85 +/- 5 mmHg to 86 +/- 4 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular effects alter early-gestation fetal renal responses to vasopressin
Authors: Ervin M. G. , Terry K. A. , Calvario G. C. , Castro R. , Ross M. G. , Leake R. D. , Fisher D. A.
Published: December 2017

Distinct receptors mediate the vascular (V1) and renal (V2) effects of arginine vasopressin (AVP). Although ovine fetal AVP-induced antidiuresis can be demonstrated in early gestation (< 120 days; term 150 days), the early-gestation fetal renal responses to AVP are variable, including increases in urine flow and glomerular filtration rate (GFR). AVP V1 receptor predominance and/or V2 receptor system immaturity may contribute to variable early-gestation renal responses to AVP. To differentiate these possibilities, we assessed early-gestation fetal V2 receptor function in the presence and absence of V1 receptor-mediated effects by comparing the responses to AVP (a combined V1-V2 receptor agonist; n = 10; 112 +/- 2 days) with the selective V2-receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP) (n = 5; 111 +/- 2 days). AVP infusion increased fetal mean arterial pressure (MAP; 36 +/- 1 to 44 +/- 2 mmHg) and decreased heart rate (197 +/- 2 to 171 +/- 3 beats/min); DDAVP infusion had no effect on MAP or heart rate. Free water clearance decreased in response to AVP (0.13 +/- 0.02 to 0.02 +/- 0.01 ml.min-1.kg-1) and DDAVP (0.21 +/- 0.04 to 0.04 +/- 0.02 ml.min-1.kg-1), and urine osmolality increased in response to both analogues (AVP: 145 +/- 4 to 283 +/- 15 mosmol/kgH2O; DDAVP: 146 +/- 5 to 244 +/- 32 mosmol/kgH2O).(ABSTRACT TRUNCATED AT 250 WORDS)
Vasopressin inhibits calcium-coupled sodium efflux system in rat brain
Authors: Kanda F. , Arieff A. I.
Published: December 2017

Centrally released vasopressin plays an important role in the regulation of brain water and electrolyte composition and can affect brain intracellular pH and ATP synthesis in vivo. In this study, we evaluated the effects of [Arg8]vasopressin (AVP) on the Na(+)-Ca2+ exchanger, an important pathway in the regulation of cell Ca2+ concentration. It was found that AVP inhibited the Na(+)-Ca2+ exchanger in rat brain synaptosomes. This effect was completely blocked by the vasopressin V1-receptor antagonist d(CH2)5[(O-Me) Tyr2, Arg8]vasopressin. In addition, the vasopressin V2-receptor agonist 1-desamino-8-D-arginine vasopressin had no effect on the Na(+)-Ca2+ exchanger in rat brain synaptosomes. Depletion of intracellular Ca2+ by caffeine also had no effect on the effect of AVP on the Na(+)-Ca2+ exchanger. Na+ uptake by other pathways was also evaluated. It was found that AVP had no effect on Na+ uptake by pathways other than the Na(+)-Ca2+ exchanger. It is concluded that AVP inhibits the Na(+)-Ca2+ exchanger in neuronal membranes through vasopressin V1 receptors. Since this pathway is important in the regulation of cell volume and cytosolic Ca2+ in excitable tissue, AVP may impair neuronal cell repolarization in the central nervous system.
Effect of ethanol on energy expenditure
Authors: Suter P. M. , Jequier E. , Schutz Y.
Published: December 2017

The thermogenic response induced by ethanol ingestion in humans has not been extensively studied. This study was designed to determine the thermic effect of ethanol added to a normal diet in healthy nonalcoholic subjects, using indirect calorimetry measurements over a 24-h period in a respiration chamber. The thermic effect of ethanol was also measured when ethanol was ingested in the fasting state, using a ventilated hood system during a 5-h period. Six subjects ingested 95.6 +/- 1.8 (SE) g ethanol in 1 day partitioned over three meals; there was a 5.5 +/- 1.2% increase in 24-h energy expenditure compared with a control day in which all conditions were identical except that no ethanol was consumed. The calculated ethanol-induced thermogenesis (EIT) was 22.5 +/- 4.7% of the ethanol energy ingested. Ingestion of 31.9 +/- 0.6 g ethanol in the fasting state led to a 7.4 +/- 0.6% increase in energy expenditure over baseline values, and the calculated EIT was 17.1 +/- 2.2%. It is concluded that in healthy nonalcoholic adults ethanol elicits a thermogenic response equal to approximately 20% of the ethanol energy. Thus the concept of the apparently inefficient utilization of ethanol energy is supported by these results which show that only approximately 80% of the ethanol energy is used as metabolizable energy for biochemical processes in healthy nonalcoholic moderate ethanol consumers.
Lactic acidosis transiently increases metabolic rate of turtle myocytes
Authors: Watson C. L. , Few W. L. , Panol G. , Jackson D. C.
Published: December 2017

We measured O2 consumption as an estimate of metabolic rate in isolated calcium-tolerant ventricular myocytes of turtles (Chrysemys picta belli) at control pH 7.8 and in the same solution brought to pH 7.4 and 7.0 with additions of lactic acid. Our aim was to test the hypothesis that lactic acidosis caused metabolic depression by initiating downregulation of Na+ channels, and thus Na(+)-K(+)-ATPase (Na+ pump) activity, which we would measure as a decrease in O2 consumption. Myocyte O2 consumption was measured in reptilian N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid-buffered Ringer solution and in nomially Na(+)- and Ca(2+)-free solution, thus estimating the Na+ pump component of metabolic rate. Lowering extracellular pH from 7.8 to 7.0 resulted in a significant increase in metabolic rate of cells in Ringer solution but not those in Na(+)- and Ca(2+)-free solution. This result was unchanged by the addition of 2 mM Ca2+ to Na(+)-free cell suspensions, indicating that the difference was due to the presence of Na+. Addition of 100 microM amiloride to cells in Ringer solution at pH 7.0 abolished the increase in O2 consumption, suggesting that the apparent increase in Na(+)-K(+)-ATPase activity was secondary to Na(+)-H+ exchange. Intracellular pH was measured using 5,5-dimethyl[14C]oxazolidine-2,4-dione. Cells treated with amiloride and those in Na(+)- and Ca(2+)-free solution did not regulate intracellular pH following acidosis and maintained basal metabolic rate. These data suggest that the Na(+)-H+ exchanger is an important contributor to intracellular pH regulation in the myocyte but increases Na+ pump activity and metabolic rate immediately following acidosis.
Use of sinoaortic denervation to study the role of baroreceptors in cardiovascular regulation
Authors: Schreihofer A. M. , Sved A. F.
Published: December 2017

To assess the role of arterial baroreceptors in cardiovascular regulation, many studies have used rats in which baroreceptor afferents have been surgically destroyed. However, interpretation of studies using sinoaortic-denervated (SAD) rats is complicated by variability in the extent of baroreceptor denervation. We have compared cardiovascular regulation in rats with total sinoaortic cardiovascular regulation in rats with total sinoaortic denervation, as assessed by the abolition of reflex changes in heart rate (HR) to increases and decreases in arterial pressure (AP), with rats that underwent the same denervation procedure but still had residual (although markedly blunted) reflex changes in HR to changes in AP. In totally SAD rats, the lability of AP was greatly exaggerated compared with sham-denervated rats, although the average AP was equivalent. In contrast, partially SAD rats had elevated AP, and although AP was more labile than in sham-denervated rats, it was less labile than in totally SAD rats. In addition, cardiovascular responses elicited by elimination of neural activity in the nucleus tractus solitarius (NTS) were qualitatively different between the two groups of rats; destruction of the NTS increased AP similarly in partially SAD rats and sham-denervated rats, whereas this treatment did not alter AP in totally SAD rats. Thus there are marked differences in SAD rats with no residual arterial baroreceptor reflex function compared with SAD rats with even a small degree of residual baroreceptor reflex function. These studies highlight the importance of carefully characterizing SAD rats used in studying the role of the baroreceptor reflex in cardiovascular regulation.
Cardiac function in fetal sheep during two weeks of hypoxemia
Authors: Kamitomo M. , Longo L. D. , Gilbert R. D.
Published: December 2017

Although several studies have examined fetal cardiac responses to acute hypoxemia, relatively little is known of the response to prolonged hypoxemia. To determine the effects of long-term hypoxemia on ovine fetal cardiac function, we measured right (QRV) and left ventricular outputs (QLV) and determined the effects of increasing preload (ventricular function curve) and afterload (arterial pressure sensitivity curve) on the left ventricle. Six days after fetal surgical instrumentation with catheters and electromagnetic flow probes (approximately 123 days gestation), we administered N2 into the maternal trachea for 14 days to reduce maternal PO2 to approximately 55 Torr (hypoxemic group, Hyp, n = 6). Normoxic animals were used as controls (Cont, n = 6). With the onset of hypoxemia, fetal arterial PO2 was reduced from approximately 27 to approximately 18 Torr. Fetal heart rate in Hyp fetuses decreased approximately 22% on day 14 compared with Cont (P < 0.05). Mean arterial pressure in the Hyp group was higher than that of Cont but not significantly so. Right and left atrial pressures were not affected by hypoxemia. QRV in Hyp fetuses was maintained on day 1 but decreased significantly by day 3 (approximately 19%) and further decreased on days 7 (approximately 28%) and 14 (approximately 34%). QLV was not depressed until day 7 (approximately 20%), with a further decrease on day 14 (approximately 38%). In association with the decreased QLV the plateau of the ventricular function curve in Hyp fetuses was depressed significantly on days 7 and 14. In contrast, the slope of the arterial pressure sensitivity curve in the Hyp group did not differ from Cont.(ABSTRACT TRUNCATED AT 250 WORDS)
Peripheral bombesin decreases gastric vagal efferent activity in part through vagal pathways in rats
Authors: Yoshida-Yoneda E. , Tache Y. , Kosoyan H. P. , Wei J. Y.
Published: December 2017

The influence of intravenous (iv) bombesin on multiunit activities recorded from the ventral gastric branch of the vagus was investigated in urethan-anesthetized rats. Consecutive injections of bombesin (0.062, 0.62, 6.2, 62, and 620 pmol iv) decreased dose dependently gastric vagal efferent discharges to 79.8 +/- 4.9, 68.3 +/- 10.2, 47.0 +/- 6.7, 41.6 +/- 4.7, and 36.5 +/- 8.9%, respectively, from preinjection levels. Saline injection had no effect. Bombesin (62 pmol iv) reduced cervical vagal efferent discharges to 25 +/- 6% before and 67 +/- 5% after bilateral cervical vagotomy distal to the recording site. Bombesin (62 and 620 pmol iv) increased gastric vagal afferent discharges by 45 and 93%, respectively. These data show that systemic injection of bombesin potently decreases gastric and cervical vagal efferent activity in part through vagal-dependent mechanisms that may involve the increase in gastric vagal afferent activity.