bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological doses of atrial peptide inhibit angiotensin II-stimulated aldosterone secretion
Authors: Metzler C. H. , Ramsay D. J.
Published: December 2017

The current study was designed to investigate the potential of atrial peptide to serve as a physiological regulator of aldosterone secretion. Conscious chronically instrumented dogs were given a constant intravenous infusion of either atrial peptide [ANP-(1-28); 5, 25, or 100 ng.kg-1.min-1] or vehicle (saline). Once steady-state conditions were achieved, angiotensin II was infused in a ramp design to stimulate aldosterone secretion (2.5-40 ng.kg-1.min-1). In the absence of atrial peptide, angiotensin II induced dose-dependent increases in plasma aldosterone concentration. In the presence of a 5-ng.kg-1.min-1 infusion of atrial peptide, the aldosterone response was reduced an average of 65 +/- 11%. When atrial peptide was infused at 25 and 100 ng.kg-1.min-1, the response was totally abolished. These results show that atrial peptide is a potent inhibitor of angiotensin II-stimulated aldosterone secretion. The results suggest that normal variations in plasma atrial peptide concentration can play an important role in the regulation of aldosterone secretion and fluid and electrolyte balance.
Cerebral blood flow, oxygenation, and carbohydrate metabolism in immature fetal sheep in utero
Authors: Gleason C. A. , Hamm C. , Jones M. D.
Published: December 2017

Studies of cerebral blood flow (CBF) and metabolism in fetal sheep have been largely confined to late gestation, a time when brain development in this species is largely complete. Few studies have been done at a time when the fetal sheep brain is in the midst of rapid differentiation and development. We studied seven fetal sheep in utero at 91 days of gestation (term = 145-150 days) 24 h after catheters were placed into the sagittal sinus, axillary artery, and inferior vena cava. We measured CBF by the microsphere method and used arteriovenous differences of O2, lactate, and glucose to calculate cerebral O2 consumption (CMRo2), fractional O2 extraction, glucose consumption, O2-glucose index (OGI), and cerebral lactate production. Compared with near-term fetal sheep, we found lower CBF (33.9 +/- 5.3 ml.100 g-1.min-1), lower glucose consumption (8.5 +/- 1.25 mumol.100 g-1.min-1), and lower CMRo2 (41.8 +/- 8.8 mumol.100 g-1.min-1). Fractional O2 extraction was 0.29 +/- 0.04, which is similar to near-term fetal sheep. There was consistent cerebral lactate production (2.45 +/- 1.58 mumol.100 g-1.min-1). The OGI was 81 +/- 16%, i.e., oxidative metabolism could account for 81% of glucose uptake. Lactate production accounts for virtually all glucose uptake exceeding that required for oxidation.
Efferent pelvic nerve activity, ganglionic filtering, and the feline bladder
Authors: Satchell P. , Vaughan C.
Published: December 2017

Ganglionic "filtering" may be responsible for muting the parasympathetic drive to the bladder during urine storage. For this process to be significant, there must be activity in preganglionic parasympathetic nerve fibers during continence. In cats, anesthetized with pentobarbital sodium, pelvic efferent nerve activity was recorded while the bladder was filled at a physiological rate. In one-half of the animals, there was no nerve activity during continence. Pelvic efferent nerve activity was observed in some animals, particularly in those with larger nonmicturating contractions. In these animals, multiple recordings from different sites in the pelvic plexus failed to provide evidence of ganglionic filtering. Ganglionic modulation of the excitatory motor drive to the bladder could not be observed during the continence process.
Responses of thalamic neurons in rats to skin cooling and hypothalamic temperature
Authors: Sakata Y. , Morimoto A. , Murakami N.
Published: December 2017

The responses of rat thalamic neurons to skin cooling were electrophysiologically examined. The responses of cold-excited neurons were classified into two types. One is a steplike response in which the activity abruptly increases with skin cooling, and the other is a graded response in which the activity gradually increases with skin cooling. The sites of these neurons were histologically identified in the ventrobasal complex of the thalamus, ventrolateral thalamus, and posterior thalamus. Two-thirds of them were found in a marginal region of the ventrobasal complex. There is no specific localization between the sites of thalamic neurons showing the steplike response and those showing the graded response. Furthermore, the effects of hypothalamic temperature on the thalamic neurons responding to skin cooling were observed. The response of thalamic neurons to cold stimulation of the skin was markedly suppressed during the hypothalamic warming. These results show that the steplike response is related to converting thermal analog signals to digital signals and that the graded response is related to relaying analog patterns of cold signals. Thermal afferent signals are modulated by hypothalamic temperature and subsequently cold sensation is modulated.
Reflex inhibition of plasma renin activity by increased left ventricular pressure in conscious dogs
Authors: Gorman A. J. , Chen J. S.
Published: December 2017

The purpose of the present study was to determine the effects of left ventricular (LV) outflow obstruction on plasma renin activity (PRA) and the contribution from afferent receptors located in the LV myocardium. In chronically instrumented, conscious dogs (n = 12), changes in PRA during a 15- to 20-mmHg decrease in arterial blood pressure were assessed during 1) intravenous infusions of nitroprusside (NP) alone and 2) infusions of NP while peak systolic LV pressure was elevated by acute ascending aortic occlusion (AAO + NP). Infusions of NP alone elicited significant increases in heart rate (24.9 +/- 5.1 beats/min; P less than 0.01) and in PRA [3.31 +/- 0.53 ng angiotensin I (ANG I).ml-1.h-1; P less than 0.01]. These were accompanied by decreases in both LV pressure (-13.8 +/- 3.6 mmHg; P less than 0.05) and left atrial pressure (-3.0 +/- 0.7 mmHg; P less than 0.05). During AAO + NP, LV pressure was elevated to an absolute level of 169.2 +/- 4.6 mmHg (+53.3 +/- 4.2 mmHg; P less than 0.001), whereas left atrial pressure was not changed. Both the hypotension-induced rise in PRA and tachycardia were significantly inhibited during AAO + NP (+0.59 +/- 0.29 ng ANG I.ml-1.h-1 and +6.3 +/- 4.6 beats/min, respectively; NS). The topical application of a local anesthetic in the region of the main coronary artery, sufficient to block the heart rate and arterial blood pressure responses to selective LV receptor stimulation by intracoronary veratridine (0.1-0.4 microgram/kg), resulted in significant increases in PRA and heart rate during AAO + NP.(ABSTRACT TRUNCATED AT 250 WORDS)
ACTH-induced hypertension in rats: fact or artifact?
Authors: Gruber K. A. , Eskridge-Sloop S. L. , Eldridge J. C. , Callahan M. F.
Published: December 2017

Evidence from numerous laboratories has shown that administration of adrenocorticotropic hormone (ACTH) to rats produces hypertension within 5 days. However, the analysis of blood pressure in these studies was by the tail-cuff technique, an acute and indirect approach. We have now administered ACTH, via a subcutaneous depot injection (5 or 10 U/day for 9 days), to chronically instrumented rats maintained in metabolic cages. Although tail-cuff measurements of arterial pressure indicated that the ACTH treatment produced hypertension, this was not confirmed by direct 24-h measurements of mean arterial pressure. There was no effect of ACTH on 24-h heart rate throughout the treatment period compared with saline-injected controls. We also examined coefficient of variation of all our measurements. None of the factors was altered by ACTH administration. However, ACTH treatment did produce a diuretic effect, further confirming previous work and providing renal, in addition to cardiovascular, evidence for the bioavailability of the ACTH depot. These results demonstrate that chronic ACTH treatment does not produce a true hypertensive state in rats but rather may enhance the cardiovascular response to the stress of the indirect arterial pressure measurement technique.
Effects of anoxia on catecholamine levels in brain and kidney of the crucian carp
Authors: Nilsson G. E.
Published: December 2017

Catecholamine synthesis requires O2. Crucian carp (Carassius carassius L.), which are extremely anoxia tolerant, were exposed to anoxia for 76 or 160 h. The brain levels of dopamine and norepinephrine (no epinephrine was found in brain) remained relatively constant even after nearly 1 wk of anoxia, indicating very well-functioning transmitter reuptake mechanisms and/or the absence of O2-independent degradation. In contrast, in the kidney (which contains chromaffin tissue), the catecholamine content (at least norepinephrine) decreased by 22-60% after 160 h of anoxia. Moreover, when anoxic crucian carps were put in normoxic water for approximately 40 min, the kidney catecholamine levels increased by 50-370%, whereas no significant effect was seen in brain. Thus, in the kidney, all that was lost during nearly 1 wk of anoxia seemed to be regained in less than 40 min of normoxia. This might reflect an adaptive strategy. Because of the limited possibility of recovering catecholamines that have been released into the bloodstream, the crucian carp chromaffin tissue might have become very good at taking the opportunities given by short contacts with O2 to rapidly renew its catecholamine store.
Control of torpor and body weight patterns by a seasonal timer in Siberian hamsters
Authors: Bartness T. J. , Elliott J. A. , Goldman B. D.
Published: December 2017

Two experiments were designed to assess whether the short-day-induced patterns of shallow daily torpor, body weight, and other seasonal responses (food intake and pelage pigmentation) exhibited by Siberian hamsters (Phodopus sungorus sungorus) are under the control of a "seasonal timekeeping mechanism" that is independent of reproductive status [testosterone, (T)]. We examined whether the patterning and expression of these seasonal responses were altered by decreases in serum T that accompany gonadal regression during the first 8 wk of short-day exposure (i.e., the "preparatory phase" of the torpor season) or by experimental increases in serum T after this phase. Short-day-housed, castrated hamsters bearing T implants had long-day levels of the hormone and did not exhibit torpor. Appropriate seasonal patterns and levels of torpor, body weight, pelage color stage, and food intake were exhibited after T implant removal although serum T was clamped to long-day levels during the preparatory phase. In animals that were gonad intact during the preparatory phase and were subsequently castrated and given T implants, torpor did not occur as long as the implants were in place. However, the patterns and levels of daily torpor, food intake, and body weight rapidly returned to appropriate seasonal values compared with the castrated, blank-implanted controls on T implant removal; these effects occurred whether the T implants were removed when torpor frequency was increasing, at its peak, or decreasing across the torpor season. T did not affect pelage color stage under any condition.(ABSTRACT TRUNCATED AT 250 WORDS)
Lack of vasopressin increases hypothalamic atrial natriuretic peptide binding sites
Authors: Castren E. , Saavedra J. M.
Published: December 2017

Atrial natriuretic peptide (ANP) binding sites were measured by quantitative autoradiography in the supraoptic and paraventricular nuclei and in the subfornical organ of hypophysectomized, adrenalectomized, and genetically vasopressin-deficient (Brattleboro) rats. Hypophysectomized and Brattleboro rats had significantly higher numbers of ANP binding sites in the supraoptic nucleus and in the magnocellular subdivision of the paraventricular nucleus than their respective controls. ANP binding density was also increased in the parvocellular subdivision of the paraventricular nucleus in hypophysectomized rats and in the subfornical organ of homozygous Brattleboro rats. When homozygous Brattleboro rats were treated with vasopressin, the density of ANP binding sites was restored to control level in the subfornical organ but not in the supraoptic or paraventricular nuclei. Adrenalectomy did not influence ANP binding in the brain areas studied. Increased ANP binding density in Brattleboro rats and after hypophysectomy in the nuclei in which vasopressin neurons are located suggest that ANP binding sites may represent physiologically active receptors and may mediate the inhibitory action of ANP on vasopressin secretion.
Renal sympathetic nerve activity and norepinephrine release in rats
Authors: Deka-Starosta A. , Garty M. , Zukowska-Grojec Z. , Keiser H. R. , Kopin I. J. , Goldstein D. S.
Published: December 2017

We examined relationships between changes in directly recorded renal sympathetic nerve activity (RSNA) and renal and total body spillover of norepinephrine into the bloodstream (RNEs and TBNEs, respectively) in anesthetized, adrenal-demedullated rats. Intravenous infusions of nitroprusside (NP) or phenylephrine (PH) produced reflexive, dose-dependent changes in RSNA. High-doses of NP significantly increased RSNA by 90%, RNEs by 155%, and TBNEs by 268%. High doses of PH significantly decreased RSNA by 37%, RNEs by 35%, and TBNEs by 33%. Ganglionic blockade with chlorisondamine decreased RSNA by 65% (P less than 0.05), RNEs by 10%, and TBNEs by 51% (P less than 0.05). There was a significant curvilinear relationship between mean changes in RSNA and mean changes in RNEs (r = 0.99). Simultaneous in vivo measurement of sympathetic nerve traffic and regional release of norepinephrine therefore may be useful in the assessment of presynaptic actions of drugs and hormones and in the evaluation of abnormal sympathetic neurotransmission in disease states.
Allopurinol kinetics in humans as a means to assess liver function: design of a loading test
Authors: Van Waeg G. , Groth T.
Published: December 2017

A six-compartment model of allopurinol and oxipurinol kinetics, after intravenous allopurinol injection in the human, is studied further to improve the blood and urine specimen collection schedule for clinical use. The effects of various error sources are also investigated by simple techniques like real data set truncation and adding normally distributed random errors to data obtained from simulation of allopurinol and oxipurinol plasma curves with preset parameters. All parameters estimation is performed with the NONLIN parameter estimation program. Main interest was focused on estimation of the fractional rate constant of transport from the central "extracellular" compartment to the metabolically active compartment. This parameter is regarded as a lumped measure of liver perfusion and liver cell membrane transport. The blood sampling schedule can be reduced to six specimens collected over 60 min, without affecting the accuracy and precision of estimated clinical parameters. The maximum allowable coefficient of variation for preanalytical errors and the analytical within-run and between-run errors are around 5, 4, and 5%, respectively. Analytical between-run bias up to 20% does not affect the estimate of the principal parameter, when both allopurinol and oxipurinol are biased in the same direction. Collection and analysis of urine samples was shown to be unnecessary.
Cold exposure reverses inhibitory effects of fasting on peripheral glucose uptake in rats
Authors: Shibata H. , Perusse F. , Vallerand A. , Bukowiecki L. J.
Published: December 2017

The effects of fasting and cold exposure on glucose uptake in skeletal muscles (tibialis anterior, quadriceps, and soleus), heart, and brown adipose tissue (BAT) were studied in conscious rats. Glucose uptake was estimated by determining the glucose metabolic index of individual tissues using the 2-[3H]deoxyglucose method. Fasting for 18 h at 25 degrees C decreased plasma glucose levels (-40%) and glucose uptake in heart (-95%) and skeletal muscles (-64-90%) but did not significantly affect glucose uptake in BAT. Fasting for 48 h did not further decrease these parameters. On the other hand, cold exposure (48 h at 5 degrees C) of fed animals did not alter plasma glucose levels but increased glucose uptake in heart (73%), skeletal muscles (126-326%), and particularly in BAT (95-fold). Remarkably, cold exposure stimulated glucose uptake in BAT and skeletal muscles of 18-h fasted rats by the same order of magnitude as in fed animals (percentagewise), thereby indicating that glucose represents an essential metabolite for shivering (muscles) and nonshivering (BAT) thermogeneses. In the heart of starved animals, the cold-induced increase in glucose uptake was even more important (8-fold) than in fed animals. Considering that cold exposure of fasted rats results in a severe insulinopenia, it is suggested that cold exposure stimulates glucose uptake in peripheral tissues primarily by enhancing glucose oxidation via insulin-independent pathways.
Effects of propranolol and pindolol on plasma ANP levels in humans at rest and during exercise
Authors: Bouissou P. , Galen F. X. , Richalet J. P. , Lartigue M. , Devaux F. , Dubray C. , Atlan G.
Published: December 2017

In attempt to elucidate whether the beta-adrenoceptor is involved in the control of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP level was measured at rest, in recumbent and upright positions, and during graded maximal ergocycle exercise in nine healthy male subjects (23 +/- 0.5 years of age) treated for 3 days with nonselective beta-blockers propranolol (150 mg/day) or pindolol (15 mg/day) or with placebo. The effects of beta-blockers, which differ by their hemodynamic actions at rest because of the intrinsic sympathomimetic activity of pindolol, were compared. Maximal O2 consumption (VO2max) during beta-blockade was not significantly different from the placebo value. Resting heart rate was not affected by pindolol treatment but was decreased with propranolol (-10 beats/min). Both beta-blockers caused a reduction in heart rate at all the exercise intensities. Mean blood pressure was not affected by beta-blockade at rest but was significantly reduced during exercise. During placebo treatment, plasma ANP increased in response to exercise intensities greater than 65% of VO2max. At 100% VO2max plasma ANP was nearly doubled (101.5 +/- 14 pg/ml) compared with the basal value in upright position (56.6 +/- 15 pg/ml). beta-Blockade caused a marked elevation in plasma ANP at all the levels of activity. Despite different hemodynamic responses to pindolol and propranolol, both beta-blockers produced similar increases in the basal level of plasma ANP. These rises were maintained in the course of exercise tests, and no significant difference was found between propranolol and pindolol. We conclude that beta-adrenoceptor mechanisms are not directly responsible for tonic and exercise-induced ANP secretion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of glycolytic enzymes during anoxia in the turtle Pseudemys scripta
Authors: Brooks S. P. , Storey K. B.
Published: December 2017

The glycolytic enzymes glycogen phosphorylase, phosphofructokinase (PFK), and pyruvate kinase (PK) were assessed in liver, heart, red muscle, and white muscle of aerobic and 5-h anoxic turtles (Pseudemys scripta) for changes in total activity and kinetic parameters. Anoxia induced statistically significant changes in these glycolytic enzymes in each of the four organs assayed. Compared with normoxic controls, anoxic liver showed a 3.3-fold increase in glycogen phosphorylase activity, a 1.5-fold increase in the PFK I50 value for citrate (concentration that inhibits initial activity by 50%), a 1.5-fold increase in the PFK Michaelis constant (Km) value for fructose 6-phosphate (P), and an increased maximal activity of PK. Anoxic heart muscle showed a 2.6-fold decrease in glycogen phosphorylase activity and, for PFK, a 1.7-fold decrease in the Km value for ATP and a twofold increase in the I50 value for citrate. In anoxic white muscle, PFK showed a fivefold lower Km value for fructose-6-P and a threefold lower activator concentration producing half-maximal activation (A50) for potassium phosphate than the aerobic enzyme form. Changes in anoxic white muscle PK included a twofold increase in the Km value for ADP and a 1.7-fold decrease in the I50 value for alanine. In red muscle, anoxia affected only the Km value for ATP, which was 50% higher than the value for the aerobic enzyme form. Fructose 2,6-diphosphate (P2) levels also decreased in heart muscle and increased in red and white muscle during anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Lateral cerebroventricular injection of neuropeptide Y stimulates feeding in sheep
Authors: Miner J. L. , Della-Fera M. A. , Paterson J. A. , Baile C. A.
Published: December 2017

We compared the effects of neuropeptide Y (NPY) injected into the lateral ventricle (LV) and periphery (ip in rats; iv in sheep) on feed and water intake. In sated rats, a bolus injection of 1.18 or 2.35 nmol of NPY administered LV, but not ip, increased (P less than 0.05) feed intake on average of 809% within 30 min of injection. In sated sheep, an LV bolus injection of 2.35 nmol of NPY increased feed intake by 154% within 30 min. Similar doses of human pancreatic polypeptide and peptide YY were less orexigenic than NPY in sheep. After 24 h, cumulative feed intakes were similar among control and peptide treatments. Intravenous injection of 2.35 nmol NPY did not increase feed intake in sheep. Water intake was stimulated (P less than 0.05) by NPY (LV injection) in both the presence and absence of feed. We propose that NPY is involved in the central regulation of consummatory behavior in sheep.
Energetics of sodium-coupled active transport mechanisms in invertebrate epithelia
Authors: Gerencser G. A. , Stevens B. R.
Published: December 2017

The Na+ gradient has been implicated as the sole or primary energy source for accumulative transport of organic solutes (e.g., sugars, amino acids) across the mucosal membrane of a variety of epithelial cells. A basic question concerning the Na+-coupled transport process in epithelia is whether the energy available from the transmucosal Na+ electrochemical difference is sufficient to sustain an accumulated organic solute steady-state level. Measurements of Na+ activities, with Na+-sensitive microelectrodes, gave accurate estimates of the Na+ electrochemical potential difference across the mucosal membrane of Aplysia californica gut. The results suggest that the transmucosal Na+ gradient can furnish sufficient energy to sustain the observed intracellular levels of the cotransported species. Many other species sustain large intracellular-extracellular gradients (less than 10(6):1) of free solutes. Theoretical models suggest that secondary active transport mechanisms in these epithelia operate by energetic multiple coupling to the Na+ electrochemical gradient; coupling coefficients of approximately 3 may represent an evolutionary optimization of these epithelial cotransporters. To properly investigate the cotransport mechanisms and energetics in invertebrate membranes, prototype mammalian vesicle experiments should be extended to the invertebrate laboratory.
Corticotropin-releasing factor attenuates interleukin 1-induced sleep and fever in rabbits
Authors: Opp M. , Obal F. , Krueger J. M.
Published: December 2017

Interleukin 1 (IL-1), a key mediator of the acute phase response, stimulates hypothalamic corticotropin-releasing factor (CRF) release. The CRF-adrenocorticotrophic hormone (ACTH)-glucocorticoid axis is a feedback for peripheral production and action of IL-1. Effects of intracerebroventricularly administered CRF on rabbit sleepwake activity, brain temperature (Tbr), and behavior and on the central effects of IL-1 [fever and excess non-rapid-eye-movement sleep (NREMS)] were studied. CRF (0.1-1.25 micrograms) dose dependently decreased NREMS and enhanced wakefulness. IL-1-induced excess NREMS was inhibited by CRF. Rapid-eye-movement sleep (REMS) suppressed by IL-1 was partially restored by 0.1 or 0.5 microgram CRF, although CRF itself did not promote REMS. Behavioral effects of intracerebroventricular CRF were relatively small, although 1.25 micrograms abolished ingestion for 3 h, suppressed rearing behavior, and increased sitting behavior. Tbr increased after CRF injection alone. After IL-1 pretreatment, however, 0.1 and 0.5, but not 1.25, micrograms CRF reduced IL-1-induced fever after several hours. These results implicate IL-1-induced CRF release as part of a negative-feedback mechanism attenuating not only peripheral IL-1 actions but also its central effects.
Cardiovascular effects of calcitonin gene-related peptide in conscious dogs
Authors: Wang B. C. , Bie P. , Leadley R. J. , Goetz K. L.
Published: December 2017

To elucidate the cardiovascular effects of alpha-human calcitonin gene-related peptide (CGRP), we infused CGRP intravenously at increasing rates of 3, 10, and 30 pmol.kg-1.min-1 during successive 15-min intervals into intact dogs, cardiac-denervated (CD) dogs, and cardiac-denervated dogs pretreated with beta-blockers. In intact dogs, the initial infusion rate of CGRP at 3 pmol.kg-1.min-1 did not produce significant hemodynamic changes, but the two higher infusion rates produced dose-dependent decreases in total peripheral resistance, mean arterial pressure, and left and right atrial pressures and produced dose-dependent increases in heart rate (HR) and cardiac output (CO). In addition, stroke volume decreased and pulmonary vascular resistance increased at the highest infusion rate. In CD dogs, CGRP produced qualitatively similar responses, although the increase in HR was markedly attenuated. The increase in CO was also attenuated, but the difference did not reach statistical significance. In CD dogs pretreated with beta-blockers, CGRP did not increase HR and the increase in CO was further attenuated. In a separate experiment, the lowest dose of CGRP (3 pmol.kg-1.min-1) was infused intravenously for 60 min in intact dogs; significant cardiovascular responses, qualitatively similar to those produced by higher rates of infusion, occurred. We conclude that CGRP is an extremely potent vasodilator and that the increase in HR is mediated primarily by autonomic reflexes.
Central interleukin 1-elicited hyperinsulinemia is mediated by prostaglandins but not autonomics
Authors: Cornell R. P.
Published: December 2017

This laboratory previously reported that centrally administered interleukin 1 (IL-1) in fasted pentobarbital-anesthetized rats elicited significant hyperinsulinemic and febrile responses. In characterizing this putative central mechanism for the regulation of pancreatic insulin secretion, hyperinsulinemia and fever elicited by IL-1 injected intravenously (iv) or intracerebroventricularly (icv) was totally eliminated by prior cyclooxygenase inhibition with indomethacin, ibuprofen, or meclofenamate but not lipoxygenase inhibition with propyl gallate or leukotriene receptor antagonism with LY 171883. Furthermore, central administration of prostaglandin E2 at 10 and 100 ng doses consistently evoked hyperinsulinemic, hypercorticotropinemic, and febrile responses in anesthetized rats maintained on isothermal pads. beta-Adrenergic and vagus nerves to the pancreatic beta-cells seemed likely candidates to mediate the enhanced secretion of insulin elicited by IL-1 acting centrally. However, pretreatment of rats with hexamethonium, propanolol, atropine, or bilateral subdiaphragmatic vagotomy all failed to reduce hyperinsulinemia after IL-1 iv or icv. This evidence suggests that the central mechanism for enhanced pancreatic insulin secretion elicited by IL-1 may depend on a humoral rather than autonomic neural efferent pathway. Moreover, the hyperinsulinemia is mediated in part by prostaglandins just like the well-studied febrile response.
Vagal cardiopulmonary baroreflex activation during phenylephrine infusion
Authors: Minisi A. J. , Dibner-Dunlap M. , Thames M. D.
Published: December 2017

Phenylephrine infusion (PE) has been used to raise arterial pressure (BP) in order to investigate reflex responses mediated by sinoaortic baroreflexes (SAB). Increases in cardiac filling pressures have been reported during PE. Our experiments determined whether PE selectively activates SAB without activation of vagal cardiopulmonary baroreflexes (CPR). We measured changes in mean BP, mean pulmonary arterial pressure (PAP), and renal sympathetic nerve activity (RSNA) during PE in alpha-chloralose-anesthetized dogs before and after sinoaortic denervation (SAD; n = 10), selective vagotomy (n = 9), or SAD and vagotomy (n = 4). PE elevated both BP and PAP in all dogs studied. In dogs with SAB and CPR intact, RSNA was reflexively inhibited (% change RSNA: -76.3 +/- 4.7). In SAD dogs, inhibition of RSNA was significantly attenuated but not abolished (% change RSNA: -27.5 +/- 11.8). This inhibition after SAD correlated closely with increases in PAP. Small BP changes (10 mmHg) were associated with insignificant changes in PAP and RSNA. Volume expansion after SAD produced changes in PAP and RSNA similar to those produced by PE. After selective vagotomy, the sensitivity (% change RSNA/mmHg change BP) of the reflex elicited by PE was significantly decreased (-2.7 +/- 0.03 pre vs. -1.8 +/- 0.12 post; P = 0.01). PE failed to change RSNA after combined SAD and vagotomy. We conclude that vagal CPR contribute to reflex inhibition of RSNA during PE except when elevations of BP are small.
Structure-function analyses of brain angiotensin control of pressor action in rats
Authors: Wright J. W. , Jensen L. L. , Roberts K. A. , Sardinia M. F. , Harding J. W.
Published: December 2017

The present investigation examined the relative pressor potencies of intracerebroventricularly infused angiotensin (ANG) II, successively shortened COOH-terminal fragments through ANG II(5-8), and the analogues [Sar1]ANG II through [Sar1]ANG II(5-8). The results indicate that ANG II, ANG III, [Sar1]ANG II, and [Sar1]ANG III were identical with respect to pressor responses in the alert free-moving rat. In addition, ANG II(3-8) and [Sar1]ANG II(3-8) exhibited 68-70% of the activity of the above compounds, whereas the activity of the shorter COOH-terminal fragments dropped to approximately 13-35%. Pressor responses caused by each of the active forms of angiotensin could be substantially reduced by pretreatment with the specific angiotensin receptor antagonist [Sar1,Thr8]ANG II (Sarthran), suggesting either that these ligands are acting at multiple receptors for ANG II and its fragments, which are all blocked by Sarthran, or that the ligands are acting at a common receptor site. These results, coupled with other recent findings, suggest that the brain angiotensin receptor may be designed to preferentially interact with ANG II and/or ANG III or other angiotensin analogues that structurally resemble ANG III such as [Sar1]ANG II. It is concluded that ANG III's importance as a centrally active ligand has been underestimated and that ANG III may be an active form of angiotensin in the brain.
Importance of prostaglandins in hypertension during reduced uteroplacental perfusion pressure
Authors: Woods L. L.
Published: December 2017

Uteroplacental ischemia causes hypertension in various species but the mechanisms involved are not known. These studies were designed to test the hypothesis that the systemic hypertension that occurs during reduced uteroplacental perfusion pressure is mediated by the prostaglandin system. Trained chronically instrumented pregnant dogs in the last third of gestation were studied. When uterine perfusion pressure was reduced to 60 mmHg for 60 min using an inflatable aortic occluder placed distal to the renal but proximal to the uterine and ovarian arteries, systemic arterial pressure increased from 95 +/- 5 to 110 +/- 7 mmHg. On another day in the same animals, the prostaglandin system was blocked with meclofenamate. Subsequent reduction of uterine arterial pressure caused no significant change in systemic pressure, from 96 +/- 4 to 99 +/- 6 mmHg, suggesting an important role for the prostaglandin system in mediating the normal response. In additional experiments, the thromboxane receptor antagonist SQ 29,548 was given. Arterial pressure averaged 94 +/- 5 mmHg after administration of SQ 29,548 and did not change significantly when uterine perfusion pressure was reduced during SQ 29,548. These data suggest that at least one component of the prostaglandin system, thromboxane, contributes to the rise in systemic arterial pressure during reduced uteroplacental perfusion pressure.
Spontaneous drinking: is it stimulated by hypertonicity or hypovolemia?
Authors: Houpt T. R. , Anderson C. R.
Published: December 2017

Ten young female pigs were allowed to eat and drink whenever they wanted, and blood samples were taken without disturbance to the pig. Samples were divided into four categories: 1) base line, i.e., taken when not drinking and not eating; 2) preprandial, i.e., taken when starting to drink just before eating; 3) postcibal, i.e., taken when starting to drink after any eating; and 4) nonprandial, i.e., taken when starting to drink but not in association with eating. Osmolality (mosmol/kgH2O), plasma protein (g/dl), and packed cell volume (%) were, respectively, as follows (mean +/- SE): base line 294.9 +/- 1.8, 6.2 +/- 0.1, and 30.0 +/- 1.2; preprandial 295.1 +/- 1.7, 6.1 +/- 0.2, and 29.7 +/- 1.4; postcibal 295.0 +/- 3.3, 6.5 +/- 0.2, and 31.7 +/- 1.3; and nonprandial 295.2 +/- 1.4, 6.3 +/- 0.1, and 30.0 +/- 1.3. None of the parameters associated with drinking were significantly different from base-line parameters, except for the postcibal rise of packed cell volume. Calculated blood volume differences from base line were as follows: preprandial 0.7 +/- 1.2% fall; postcibal 0.2 +/- 1.7% increase; and nonprandial 0.8 +/- 0.9% fall. It is unlikely that either plasma hypertonicity or hypovolemia stimulates drinking under spontaneous conditions.
Angiotensin augments epinephrine release in pithed rats fed a low-sodium diet
Authors: Vollmer R. R. , Corey S. P. , Meyers S. A. , Stricker E. M. , Fluharty S. J.
Published: December 2017

In confirmation of previous studies, the amount of epinephrine released into blood during electrical stimulation of the thoracolumbar region of the spinal cord in pithed rats on a low-sodium diet (0.01% sodium by weight of diet for 1 mo) was significantly greater than that observed in rats on a normal sodium diet (0.3% sodium by weight of diet). The present work assessed the extent to which endogenously formed angiotensin II influences this neurally mediated adrenal epinephrine release. The augmented release of epinephrine in rats maintained on the low-sodium diet appeared to depend on circulating angiotensin II because blockade of angiotensin II receptors with saralasin decreased the epinephrine release in these animals but not in rats maintained on the normal diet. Similar results were obtained when the renin-angiotensin system was blocked with the converting-enzyme inhibitor captopril. Adrenal epinephrine content was not affected by the dietary sodium intake; however, the catecholamine synthetic capacity was augmented as indicated by a significant induction of tyrosine hydroxylase. In addition, the adrenal medullary angiotensin II receptor density was significantly elevated in animals on the low-sodium diet. These results demonstrate that endogenous angiotensin II is capable of providing a positive modulatory influence on neurally mediated release of adrenal epinephrine, an effect that may require a chronic activation of the renin-angiotensin system as occurs naturally with restricted dietary sodium intake.
Cardiovascular effects of opioid antagonist naloxone in rostral ventrolateral medulla of rabbits
Authors: Morilak D. A. , Drolet G. , Chalmers J.
Published: December 2017

We have examined the influence of endogenous opioids on the basal and reflex control of arterial blood pressure in the pressor region of the rostral ventrolateral medulla (RVLM) of chloralose-anesthetized rabbits. We tested basal effects both in intact animals and after hypotensive hemorrhage. Bilateral administration of the opiod antagonist naloxone (20 nmol, 100 nl) directly into the RVLM induced a gradual and prolonged increase in mean arterial pressure (MAP) (+17 +/- 2 mmHg). This was preceded by a brief and mild depressor effect (-9 +/- 3 mmHg), which was attributable to a transient reduction in excitability immediately after naloxone injection. When naloxone was administered into the RVLM after hemorrhage (20 ml/kg), it improved recovery of MAP relative to saline controls, again producing a gradual, prolonged pressor response (+29 +/- 5 mmHg). The effect of naloxone on a baroreflex in intact animals was only transient, with a brief, nonsignificant attenuation of the reflex depressor response to aortic nerve stimulation. We conclude that endogenous opioids exert a tonic inhibitory influence on RVLM pressor neurons and that this input remains active after hemorrhage. The RVLM may thus be one site for the beneficial effects of naloxone in preventing circulatory decompensation after hemorrhage. In contrast, opioid neurons are not an essential component of baroreflex-mediated sympathoinhibition in the RVLM.
Antiserum against tumor necrosis factor enhances lipopolysaccharide fever in rats
Authors: Long N. C. , Kunkel S. L. , Vander A. J. , Kluger M. J.
Published: December 2017

The role of tumor necrosis factor (TNF, cachectin), a putative endogenous pyrogen, was investigated by comparing fever and plasma TNF levels after the intraperitoneal and intramuscular injection of 10 micrograms/kg lipopolysaccharide (LPS) into male Sprague-Dawley rats and by neutralization of endogenous TNF using TNF antiserum. An intraperitoneal injection of LPS caused a biphasic fever that lasted approximately 6.5 h. TNF levels in these rats peaked at 657 +/- 222 U/ml at 1 h then declined to virtually undetectable levels by the fourth hour. The intramuscularly injected animals showed a lower monophasic fever and low sustained TNF levels (40 +/- 10 U/ml at 1 h, 18 +/- 11 U/ml at 4 h). In a second study, an antiserum that had been shown to neutralize rat TNF was injected intraperitoneally 2 h before the intramuscular injection of 10 micrograms/kg LPS. Control rats were injected with normal rabbit serum before LPS. During the second hour after the injection of LPS, the animals that received the antiserum developed fevers that tended to be lower than those seen in the rats that were injected with control serum (0.33 +/- 0.06 vs. 0.58 +/- 0.1), although this difference was not significant. However, during the third through eighth hours after LPS, the antiserum-injected rats had mean body temperatures that were significantly higher than those of the control rats (1.62 +/- 0.11 vs. 1.07 +/- 0.09; P = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic effects on thyroxine 5'-deiodinase in brown adipose tissue of lean and ob/ob mice
Authors: Kates A. L. , Zaror-Behrens G. , Himms-Hagen J.
Published: December 2017

Genetically obese, ob/ob, mice have an impaired capacity to increase the level of thyroxine 5'-deiodinase (T5'D) in their brown adipose tissue (BAT) when they are exposed to cold. Yet they are able to secrete norepinephrine (NE) from the nerves of their BAT in response to cold and are apparently refractory to this action of NE. The principal objective was to find out whether injected NE could increase T5'D in BAT of the ob/ob mouse. A secondary objective was to elucidate the nature of the adrenergic receptor(s) involved in this response in lean and ob/ob mice. Injection of NE increased T5'D in BAT of lean mice within 3 h. It also increased T5'D in BAT of ob/ob mice but to a lesser extent. Basal T5'D activity in BAT of ob/ob mice was greater than that seen in BAT of lean mice because of the greater size of the tissue. Neither isopropylnorepinephrine nor phenylephrine alone could increase T5'D activity, but a combination increased it almost as well as did NE, although to a lesser extent in ob/ob mice than in lean mice. Both a beta-adrenergic antagonist (propranolol) and an alpha 1-adrenergic antagonist (prazosin) could inhibit the effect of NE. The acute effect of NE on metabolic rate of intact mice also involves an action of both beta- and alpha 1-adrenergic receptors. The beta-adrenergic component appears to be defective in the ob/ob mouse.
Ventromedial hypothalamic lesions abolish compensatory reduction in energy expenditure to weight loss
Authors: Vilberg T. R. , Keesey R. E.
Published: December 2017

Weight loss through caloric restriction produces compensatory reductions in the whole body energy expenditure of normal rats. The present experiment determined whether rats who had become obese after ventromedial hypothalamic (VMH) lesions displayed this metabolic defense of body weight. Obese VMH-lesioned and normal-weight control female rats were assigned to one of three weight maintenance conditions (100, 90, and 80% of previously maintained body weight). Postabsorptive oxygen consumption was then measured by open-circuit respirometery while, simultaneously, behavioral activity was measured by stabilimeter. A marked decline in resting energy expenditure and behavioral activity, seen in control rats after weight loss, was absent in VMH-lesioned rats. These results suggest that VMH lesions impair the ability to adjust energy expenditure in response to alterations in nutritional status, a response that normally serves to stabilize body weight at a regulated level.
Regulation of plasma atrial natriuretic peptide by the central nervous system
Authors: Rauch A. L. , Callahan M. F. , Buckalew V. M. , Morris M.
Published: December 2017

The anterior ventral region of the third ventricle (AV3V) is a major central site in the regulation of cardiovascular and renal function. To examine the role of the central nervous system in the regulation of atrial natriuretic peptide (ANP) secretion, the effect of lesions in this region on basal, volume-stimulated, and osmotic-stimulated plasma ANP was determined. Basal levels of plasma ANP were not different in sham- and AV3V-lesioned rats. Volume expansion with a continuous infusion of saline or with a bolus administration of saline increased plasma ANP in sham-lesioned rats. In AV3V-lesioned rats, continuous infusion of saline had no effect on plasma ANP, and a bolus administration of saline decreased plasma ANP. Osmotic stimulation with hypertonic saline increased plasma ANP in sham-lesioned rats but had no effect on plasma ANP in AV3V-lesioned rats. These results suggest that the central nervous system is involved in the regulation of ANP secretion and that altered ANP regulation may contribute to the cardiovascular and renal deficiencies in AV3V-lesioned rats.
Sleep regulation in rats during early development
Authors: Alfoldi P. , Tobler I. , Borbely A. A.
Published: December 2017

Sleep states and power spectra of the electroencephalogram (EEG) were determined in freely moving young rats. Recordings during 24 h were obtained from the same animals at three different ages. Already at the age of 23 days waking predominated in the 12-h dark period. Rapid-eye-movement sleep (REMS) declined between the age of 23 and 40 days. Its 24-h maximum was situated in the dark period at 23 and 29 days of age and in the light period at 40 days. Slow-wave activity (SWA; 0.75-4.0 Hz) of the non-REMS (NREMS) EEG showed marked age-related changes: a declining trend in the 12-h light period was absent at 23 days, moderate at 29 days, and prominent at 40 days. At 23 days, SWA progressively declined within ultradian sleep episodes and at 24 days was massively increased after 2-h sleep deprivation (SD). At the age of 30 days, 6-h SD induced much smaller changes. The distinct 24-h pattern of high-frequency activity (10.25-25.0 Hz) was present at all ages and may represent an EEG correlate of a circadian process. We conclude that homeostatic mechanisms regulating NREMS intensity are already operative a few days after weaning.
Pituitary-adrenal and adrenomedullary responses to noise in awake dogs
Authors: Engeland W. C. , Miller P. , Gann D. S.
Published: December 2017

Experiments characterized the dynamics of the pituitary and adrenocortical response to noise in awake dogs to determine if a dissociation exists between changes in plasma bioactive (bio) adrenocorticotropic hormone (ACTH) and immunoreactive (ir) ACTH. In addition, experiments determined the temporal relationship between cardiovascular, adrenomedullary, and adrenocortical responses induced by the acute presentation of noise. Trained dogs were prepared chronically with adrenal venous and femoral arterial cannulas. Experiments were done 48-96 h postsurgery and consisted of presentation of noise (75 dB; 0.25-8 kHz) for 3 min (n = 6) or of blood sampling alone (n = 5). In response to noise, mean arterial pressure and heart rate increased at 30 s and returned to base line at 4 min. Adrenal secretion of epinephrine and norepinephrine increased at 1 min and remained elevated until 4 min. Adrenal blood flow increased from 2 to 4 min as the result of a parallel increase in adrenal vascular conductance. Plasma bioACTH increased from 6 to 15 min in parallel with that of plasma irACTH. Before noise, the ratio of bioACTH to irACTH was 0.2-0.3, but the absolute change in bioACTH and irACTH after noise was not different. The increase in plasma ACTH occurred concomitant with or preceded an increase in cortisol secretion. Blood sampling alone caused no change in any variable. These data show that unexpected noise evokes a sequence of responses with rapid onset that includes tachycardia, hypertension, and increases in adrenomedullary secretion and adrenal vascular conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
Vasopressin and atrial natriuretic peptide release in cardiopulmonary denervated dogs
Authors: Shiraishi Y. , Fujimura S. , Handa M. , Kimura T. , Ota K. , Nakada T.
Published: December 2017

To assess the effect of cardiopulmonary denervation on the release of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP), either hemorrhage (1.0 ml.kg-1.min-1, for 40 min) or an infusion of 3% dextran in lactated Ringer solution (RL) (3% dextran in RL, 1.0 ml.kg-1.min-1, for 40 min) was carried out in chronic cardiopulmonary denervated (CPD, n = 7) and sham-operated (SO, n = 7) dogs under anesthesia. Plasma AVP increased significantly in both groups during hemorrhage, but its rise was significantly attenuated in CPD dogs. Plasma ANP decreased similarly during hemorrhage in both groups. An infusion of 3% dextran in RL decreased significantly plasma AVP during its whole period in SO dogs, but AVP release was only suppressed in the late period in SO dogs. Plasma ANP increased significantly during its infusion in both groups. These results indicate that cardiopulmonary denervation may attenuate the release of AVP in response to either hemorrhage or blood volume expansion but may not affect the release of ANP in response to the blood volume change. Moreover, a large increase in plasma ANP may attenuate the release of AVP.