bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal catecholamine responses to maternal hypoglycemia
Authors: Harwell C. M. , Padbury J. F. , Anand R. S. , Martinez A. M. , Ipp E. , Thio S. L. , Burnell E. E.
Published: December 2017

The present studies were designed to determine the fetal catecholamine and metabolic responses to insulin-induced maternal hypoglycemia. Maternal hypoglycemia was induced by a primed constant infusion of insulin and glucose administered to pregnant ewes to maintain maternal glucose at 20-25 mg/dl. Maternal and fetal samples for measurement of catecholamine, glucose, and free fatty acid levels and arterial blood gas analysis were collected before insulin infusion and at intervals thereafter for 6 h. Maternal and fetal plasma catecholamine levels increased significantly in response to hypoglycemia (analysis of variance, P less than 0.01). Fetal insulin and glucagon levels did not change despite a 50% reduction in fetal whole blood glucose concentration. Fetal free fatty acid levels increased significantly during hypoglycemia (P less than 0.05). There were no significant changes in maternal or fetal heart rate, blood pressure, or arterial blood gases during hypoglycemia. These results suggest that the fetus is capable of responding to hypoglycemia with an increase in catecholamine and free fatty acid levels. These results are consistent with the interpretation that the fetus is able to mobilize alternative energy substrates in response to maternal insulin-induced hypoglycemia.
Effects of compartmental fluid repletion on heat-induced limb vasodilation in dehydrated baboons
Authors: Ryan K. L. , Proppe D. W.
Published: December 2017

Dehydration attenuates the increase in hindlimb blood flow produced by environmental heating (EH) in baboons. This study explored whether intravascular volume repletion alone was sufficient to remove this dehydration-induced attenuation. In six unanesthetized, chronically instrumented baboons, the increases in hindlimb blood flow during EH were measured under these conditions: euhydrated, dehydrated (64-68 h of water deprivation) without fluid replenishment, and dehydrated with intravenous fluid replenishment by either 6% high-molecular-weight dextran solution (to replenish vascular volume) or hyperosmotic saline (to replenish vascular and interstitial fluid volumes). EH consisted of acute exposure to ambient temperatures of 38-42 degrees C until core temperature (Tc) reached 39.5 degrees C. During dehydration without fluid replenishment the increments in mean iliac artery blood flow (MIBF) and iliac vascular conductance (IVC) produced by EH (i.e., value at Tc = 39.5 degrees C - pre-EH value) were reduced by 39 and 44%, respectively. After infusion of a volume of dextran solution equal to blood volume lost during dehydration, the increment in MIBF during EH was partially restored to the euhydrated level, but the increment in IVC remained at the dehydrated level. Infusion of hyperosmotic saline during dehydration completely restored the increases in MIBF and IVC during EH to euhydrated levels. Thus restoration of normal blood volume alone in dehydrated baboons does not completely restore normal hindlimb vasodilation during EH.
Contribution of brain distortion and displacement to CSF dynamics in experimental brain compression
Authors: Schettini A. , Walsh E. K.
Published: December 2017

The present study was designed to determine the contribution of brain distortion and displacement to changes in cerebrospinal fluid (CSF) dynamics [pressure-volume index (PVI), compliance (C), and outflow resistance (Ro)] during progressive brain compression and the effect of compression on brain mechanical properties. In 10 dogs measurements were made of CSF dynamics, brain elastic behavior, cerebral perfusion pressure, local cerebral blood flow, and suprainfratentorial intracranial pressure (ICP) during the incremental expansion of a supratentorial extradural balloon. PVI appeared more as a measure of the compressibility of the cerebral vascular compartment than of intracranial bulk compliance. Reciprocal changes in CSF dynamics behaved as expected when the balloon expanded predominantly supratentorially causing a moderate increase in ICP. A significant increase in ICP, however, caused a rise in PVI and a decrease in compliance. Under these conditions PVI alone could not differentiate between a falling cerebral perfusion pressure and an increasing suprainfratentorial ICP gradient. In contrast, the compliance decreased with balloon expansion while the outflow resistance showed an inverse correlation with compliance and a linear correlation with baseline ICP; Go, an elastic response parameter, consistently decreased, implying that C, Ro, and Go can be used as a trend of intracranial compensatory reserve during intracranial mass expansion.
Influence of C-ANF receptor and neutral endopeptidase on pharmacokinetics of ANF in rats
Authors: Chiu P. J. , Tetzloff G. , Romano M. T. , Foster C. J. , Sybertz E. J.
Published: December 2017

The role of C-atrial natriuretic factor (ANF) receptors and neutral endopeptidase (NEP) in the pharmacokinetics and hydrolysis of 125I-labeled ANF was evaluated in rats by using C-ANF and SCH 39370 to block the nonenzymatic and enzymatic pathways, respectively. After a bolus injection of 125I-ANF, the resulting area under the plasma concentration curve (AUC) with C-ANF treatment was seven times the control value with regard to trichloroacetic acid-precipitable (TCA-ppt) radioactivity (intact ANF). SCH 39370 tended to increase AUC, but the changes were not significant. Nevertheless, SCH 39370 suppressed the appearance of TCA-soluble radioactivity (hydrolytic products), indicating that in vivo inhibition of ANF degradation had occurred. SCH 39370 plus C-ANF produced a 15-fold increase in AUC for TCA-ppt radioactivity and a reduction in plasma TCA-soluble radioactivity. High-performance liquid chromatography (HPLC) analysis confirmed that combination treatment increased intact ANF and reduced hydrolytic products in the plasma. SCH 39370 reduced clearance (C) without altering volume of distribution in steady state (Vss) and half-life (t1/2). C-ANF decreased both C and Vss leading to a fourfold increase in t1/2, which was further prolonged by SCH 39370 (7.5 times control). Bilateral nephrectomy caused a proportionally similar decrease in Vss and C without changing t1/2, suggesting significant extrarenal metabolism of ANF. SCH 39370 systemically inhibits ANF hydrolysis; the resulting increase in ANF, however, is masked by the great capacity of ANF clearance receptors but can be revealed with excess C-ANF, suggesting that the plasma ANF concentrations are determined by the interplay of the C-ANF receptor and NEP systems.
Responses of spinoreticular cells to graded increases in renal venous pressure
Authors: Ammons W. S.
Published: December 2017

Previous work established that occlusion of the renal vein excites spinoreticular tract (SRT) neurons of the cat. The present study was designed to determine the relationship between renal vein pressure level and SRT cell activity. Experiments were performed on 40 cats that were anesthetized with alpha-chloralose. Sixty SRT neurons in the T12-L2 segments were tested for responses to a renal vein pressure (RVP) of 60 mmHg. Twenty-three cells responded with an increase in activity. Stimulus response relationship for these cells were determined over the RVP range of 10-80 mmHg. RVP thresholds averaged 25 +/- 3 mmHg. Above this level greater increases in RVP were associated with greater increases in neuronal activity. At RVP of 80 mmHg cell activity increased from 4 +/- 2 to 21 +/- 5 spikes/s. Cells with both A delta- and C-fiber renal afferent inputs had significantly greater responses and lower thresholds than cells with only A delta input. Renal vein occlusion evoked increases in blood pressure. At a renal vein pressure of 80 mmHg, pressor responses averaged 16 +/- 5 mmHg. No significant changes in heart rate were observed. The results demonstrate that SRT cells are capable of encoding the level of RVP. Such responses may be important for grading of reflexes of renal origin that require supraspinal circuitry.
Interaction of vasopressin and opioids during rapid hemorrhage in conscious rabbits
Authors: Schadt J. C. , Hasser E. M.
Published: December 2017

We investigated possible interactions between arginine vasopressin (AVP) and endogenous opioid peptides during rapid hypotensive hemorrhage and subsequent opioid receptor blockade in conscious rabbits. Plasma AVP concentration did not change after normotensive hemorrhage but increased after hypotensive hemorrhage. Blockade of V1-AVP receptors (AVPX) did not affect prehemorrhage arterial pressure, heart rate, or hindquarter blood flow and vascular resistance. AVPX did not alter the hemodynamic response to hemorrhage or the blood loss required to reduce mean arterial pressure to less than 40 mmHg. However, hindquarter blood flow was higher and mean arterial pressure and hindquarter resistance lower after hypotensive hemorrhage in AVPX-treated animals. These differences were maintained after naloxone or saline injection. Naloxone increased mean arterial pressure and hindquarter resistance and decreased heart rate with or without AVPX. At 2 min postinjection, plasma AVP values were greater after saline than after naloxone. When naloxone's pressor response was reduced by alpha-adrenergic blockade, plasma AVP values were higher after naloxone than after saline. Thus AVP was not vital to maintenance of blood pressure during rapid normotensive hemorrhage or to the abrupt decrease in arterial blood pressure and resistance after rapid hypotensive hemorrhage. AVP release was important to spontaneous recovery from acute hypotensive hemorrhage but only of minor importance to naloxone's pressor response. Finally, AVP release appeared to be inhibited by endogenous opioids during acute hemorrhagic hypotension.
Characterization of renal alpha-adrenoceptor subtypes in sheep during development
Authors: Gitler M. S. , Piccio M. M. , Robillard J. E. , Jose P. A.
Published: December 2017

Intrarenal arterial infusion of alpha 1-adrenergic agonists decreases renal blood flow, glomerular filtration rate, and water and sodium excretion to a greater extent in fetus and newborn than in adult sheep. In vitro renal vascular effects of alpha 1- and alpha 2-adrenergic agonists are also greater in fetus than newborn or adult. The present studies were designed to examine the ontogeny of renal alpha-adrenoceptor subtypes in sheep for whom the renal effects of alpha-adrenergic agonists have been described at similar postconceptional ages. With the use of radioligand-binding techniques, specific binding of [3H]prazosin (alpha 1-adrenergic antagonist), [3H]idazoxan, and [3H]rauwolscine (alpha 2-adrenergic antagonists) was studied in fetus, lamb, and adult sheep kidneys. The specific binding of the three radioligands was greatest in fetal and least in adult kidneys. Analysis of Scatchard plots revealed a greater renal alpha 1-adrenoceptor density in fetuses than in lamb or adults. Renal alpha 2-adrenoceptor density was also greater in fetuses than in lambs. These studies suggest that the increased renal alpha 1- and alpha 2-adrenergic effects in fetal sheep are related to increased alpha-adrenoceptor density. Competition experiments and rank adrenergic antagonist potency suggested the presence of only the alpha 1b-adrenoceptor in fetal and adult sheep kidneys. The alpha 2-adrenoceptor that was found only in the fetal sheep had a low affinity to rauwolscine, which is unlike that described in most species for alpha 2-adrenoceptors.
Brain oxytocin receptors mediate corticotropin-releasing hormone-induced anorexia
Authors: Olson B. R. , Drutarosky M. D. , Stricker E. M. , Verbalis J. G.
Published: December 2017

Central administration of corticotropin-releasing hormone (CRH) is known to inhibit food intake and stimulate pituitary oxytocin (OT) secretion in rats. These experiments addressed the possibility that the inhibition of food intake that follows central CRH administration is mediated through oxytocinergic pathways. Male food-deprived rats, with stable baseline food intakes after intracerebroventricular (icv) injections of artificial cerebrospinal fluid, received 150 pmol of CRH icv. Food intake was inhibited by 62 +/- 5% during a 90-min test period. Pretreatment with 9 nmol of the OT antagonist [d(CH2)5, Tyr(Me)2, Orn8]vasotocin icv completely eliminated the inhibition of food intake produced by icv CRH. In contrast, pretreatment with the OT-receptor antagonist did not significantly alter pituitary secretion of adrenocorticotropic hormone and OT stimulated by icv CRH. The results of these experiments implicate OT as a possible central mediator of CRH-induced anorexias in rats, particularly those that are accompanied by stimulation of neurohypophysial OT secretion.
Sympathoadrenal activation in sinoaortic-denervated rats following endotoxin
Authors: Zhou Z. Z. , Wurster R. D. , Qi M. , Jones S. B.
Published: December 2017

We evaluated the role of the baroreceptor reflex in mediating the sympathoadrenal activation during endotoxicosis, using acutely as well as chronically denervated rats. Three groups of experiments were conducted. In the first experiment, hemodynamic and plasma catecholamine responses following endotoxin (5 mg/kg iv) were measured in alpha-chloralose-anesthetized rats with acute sinoaortic baroreceptor denervation (SAD) or sham operation. In the second experiment, chronically sinoaortic-denervated rats and sham controls were used and experiments were conducted as in acute preparations. In the third experiment hydralazine (1 mg/kg iv) was given to chronically denervated rats and sham controls to evaluate the singular contribution of hypotension-evoked baroreflex disinhibition in the absence of endotoxin. In both acute and chronic preparations, endotoxin induced marked elevation of plasma norepinephrine and epinephrine in the presence as well as the absence of arterial baroreceptors (P greater than 0.05). Plasma catecholamines were significantly increased by hydralazine-induced hypotension in the sham group, but this elevation was far less than that induced by endotoxin. Hypotension alone did not significantly increase plasma catecholamines in SAD rats. These results suggest that the baroreflex is not the major factor in mediating sympathoadrenal activation during endotoxicosis and that non-baroreflex mechanisms may be involved in stimulating such activation.
Time course of effects of preloads high in fat or carbohydrate on food intake and hunger ratings in humans
Authors: Rolls B. J. , Kim S. , McNelis A. L. , Fischman M. W. , Foltin R. W. , Moran T. H.
Published: December 2017

A high-carbohydrate (CHO) yogurt (81% CHO) and a high-fat yogurt (65% fat), containing similar levels of protein, were given in equal volumes as preloads to 14 normal-weight, nondieting males and 14 normal-weight, nondieting females. The yogurts were formulated to have similar energy densities and sensory properties, so that differences in responses to the preloads would depend on postingestive physiological effects. Three intervals (30, 90, and 180 min) between the preloads and a self-selection meal consisting of a variety of foods were utilized. The self-selection meal was served at the subject's normal lunchtime under all conditions. In the 30-min-delay condition, subjects accurately compensated for the calories in the preloads compared with a no-preload condition, but as the interval increased, compensation was less precise. No significant differences in subsequent food intake were found between the high-CHO and high-fat yogurts at any time interval. Also, there were no differences in ratings of hunger and fullness between the yogurts. The macronutrient composition of the preloads did not affect the types of foods, or macronutrients, consumed at lunch.
Volume-activated taurine efflux from skate erythrocytes: possible band 3 involvement
Authors: Goldstein L. , Brill S. R.
Published: December 2017

In a previous study (L. Goldstein, S.R. Brill, and E.V. Freund, J. Exp. Zool. 254: 114-118, 1990) it was suggested that volume-activated (VA) taurine efflux from skate (Raja erinacea) erythrocytes might involve the anion exchanger band 3. The aim of the present study was to obtain further evidence for (or against) this possibility. We found that in addition to stilbene disulfonates, two other band 3 inhibitors, N-(azido-2-nitrophenyl)-2-amino sulfonic acid (NAP)-taurine and niflumic acid, also inhibit VA taurine efflux. In addition, there is a close relationship between the dose-response curves for 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid inhibition of VA taurine efflux and sulfate efflux. Furthermore, taurine influx, as well as efflux, is activated by volume expansion, as would be expected with transport facilitated by band 3. However, sulfate (a known band 3 substrate) efflux is not activated by volume expansion, and sulfate influx is only activated minimally, but sulfate does inhibit VA taurine uptake. Thus there is considerable evidence in favor of the involvement of band 3 in VA taurine efflux, but the issue of the sulfate fluxes remains to be resolved.
Time course of renal responses to greater splanchnic nerve stimulation
Authors: Van Vliet B. N. , Smith M. J. , Guyton A. C.
Published: December 2017

The objective of the present study was to describe the time courses of renal responses during renal sympathetic stimulation and to determine whether the kidney can provide a sustained response to sympathetic stimulation for 3 h. In four pentobarbital sodium-anesthetized dogs, stimulation (3.3 Hz) of a greater splanchnic nerve (GSN) on one side caused reductions in renal blood flow (RBF) and sodium excretion (UNaV) of both stimulated and contralateral-denervated kidneys, plus an increase in plasma renin activity (PRA). During continued stimulation, RBF partially recovered, but UNaV fell to less than 5% of control and PRA rose and remained at least eight times above control. In nine dogs, a single GSN was stimulated after ipsilateral adrenal medullectomy and ligation of the splanchnic circulation. The acute response to GSN stimulation was now confined to the ipsilateral kidney. Ipsilateral RBF fell by 32 +/- 10% but returned to 85 +/- 5% of control values by the end of the stimulation period. Contralateral RBF fell slowly by approximately 10%. Ipsilateral and contralateral UNaV fell to 34 +/- 10 and 43 +/- 11% of control values, respectively. PRA increased rapidly at the onset of GSN stimulation and remained at least 2.8 times control levels. After stimulation, RBF, UNaV, and PRA returned toward control levels. These results confirm the findings of others that the response of the renal vasculature to sympathetic stimulation is mainly transient. However, they additionally demonstrate a strong and sustained decrease in UNaV lasting for the total 3-h period of sympathetic stimulation.
Respiratory responses to focal and generalized seizures in cats
Authors: Paydarfar D. , Eldridge F. L. , Scott S. C. , Dowell R. T. , Wagner P. G.
Published: December 2017

We studied the effects on breathing of seizures induced by focal injection of penicillin G into the parietal cortex in 13 anesthetized cats. Electrocorticograms, ventilation, end-tidal PCO2, and intrapleural and arterial pressures were monitored; changes of these variables were related to the stages of motor seizure. The first respiratory responses, tachypnea and hyperpnea, usually occurred before any peripheral muscular contractions developed. Progression of the seizure was always accompanied by further tachypnea and hyperpnea. The hyperpnea associated with all stages of seizure activity resulted in hypocapnia, which was sustained even during prolonged tonic-clonic motor convulsions that caused a threefold increase of metabolic rate. The extreme tachypnea of tonic generalized convulsions led to increased end-expiratory lung volume because of dynamic hyperinflation associated with very short expiratory durations in the tonic phase. We suggest that the profound effects of seizures on respiration are by feedforward mechanisms from the cortical focus itself and from subcortical circuits, such as hypothalamus, that become involved during seizure propagation and generalization. Peripheral respiratory feedback mechanisms are not important for the genesis of seizure-induced hyperpnea.
Effect of angiotensin II in ventrolateral medulla of spontaneously hypertensive rats
Authors: Muratani H. , Averill D. B. , Ferrario C. M.
Published: December 2017

The spontaneously hypertensive rat (SHR) exhibits an enhanced activity of the peripheral sympathetic and brain renin-angiotensin systems. In the present experiments, we evaluated the cardiovascular response of angiotensin II (ANG II) microinjected in the rostral (RVLM) and the caudal (CVLM) ventrolateral medulla of age-matched (14-16 wk old) SHR and Wistar-Kyoto (WKY) rats. Responses of mean arterial pressure (MAP) and heart rate (HR) to microinjection of ANG II (5, 20 and 100 pmol) into histologically verified sites of the RVLM and CVLM were compared with those obtained by injections of the excitatory agent L-glutamate (2 nmol) at the same site. In both strains, ANG II elicited dose-dependent pressor responses in the RVLM and depressor responses in the CVLM, both of which peaked at a dose of 20 pmol. The magnitude of the fall in MAP produced by injections of ANG II into the CVLM were significantly (P less than 0.01) greater in SHR than in WKY group. In contrast, peak pressor responses elicited by injection of ANG II into the RVLM were of similar magnitude in the two groups. When compared with the MAP response produced by L-glutamate injections, responses to ANG II microinjection were slower in onset, and the latency to the peak response was longer. Ganglionic blockade with hexamethonium bromide prevented the effect of ANG II injection in the RVLM. This study provides evidence that ANG II acts as an excitatory agent at sites within the ventrolateral medulla that determine the vasomotor control of blood pressure in both normotensive and hypertensive rats.
Growth hormone accelerates tubular acid secretion
Authors: Welbourne T. C. , Cronin M. J.
Published: December 2017

The effect of growth hormone on tubular H+ secretion by the hypophysectomized and intact rat was studied in the isolated functioning kidney. Net acid secretion was estimated as the sum of HCO3- absorption plus NH+4 excretion. Kidneys from either intact or hypophysectomized rats were isolated and perfused over a 90-min time course during which either recombinant human growth hormone (GH), insulin-like growth factor-1 (IGF-1), porcine insulin, or vehicle was added; hormone response was then compared with the time controls. Compared with kidneys from intact rats, hypophysectomized rat kidneys exhibited a marked acidification defect, net H+ secretion, 13,530 +/- 600 vs. 17,860 +/- 810 (SE) nmol/ml of glomerular filtrate (GF). Administering GH (50 nM) increased net H+ secretion within 15 min in both hypophysectomized and intact groups to a maximum of 17,950 +/- 910 and 20,960 +/- 1,100 nmol/ml GF, respectively; neither insulin nor IGF-1 (50 nM) was able to mimic GH's effect. Addition of 1 mM amiloride completely abolished the GH-accelerated acid secretion and greater than 70% of the basal net acid secretion rate. Furthermore, GH-enhanced volume absorption was also abolished by amiloride, although neither NaCl nor glutamine absorption was affected. GH-accelerated acid secretion and coupled volume absorption could be observed at concentrations as low as 3.5 nM with half-maximal effect at 12 nM, which is within the range of GH concentration achieved during episodic GH surges. Finally administering GH in vivo to hypophysectomized rats enhanced net acid secretion and urinary acidification, consistent with accelerated tubular H+ secretion as one physiological expression of GH action.
Bradykinin increases myocardial contractility: relation to the Gregg phenomenon
Authors: Munch P. A. , Longhurst J. C.
Published: December 2017

Bradykinin (BK) is reportedly produced in the heart during ischemia. Because BK has been shown to activate cardiac afferent nerves thought to be nocioceptors, we tested whether BK might alter myocardial shortening, which potentially could contribute to afferent nerve stimulation. In open-chest dogs, BK (1-10 micrograms) was injected into the left anterior descending (LAD) coronary artery while wall motion in the LAD and control circumflex regions was monitored. Wall motion was measured with midwall segment gauges (sonomicrometer crystals) placed in the hoop direction. Blood pressure, heart rate, left ventricular pressure, first derivative of left ventricular pressure, and LAD coronary flow also were monitored. At 15-20 s after injection, which was before circulation of the peptide caused blood pressure to change, BK decreased maximum end-diastolic and minimum end-systolic segment lengths and increased maximum shortening fraction in LAD region. No change was observed in circumflex region. The response was not eliminated by bilateral vagotomy or subsequent stellate ganglionectomy, indicating that it was not neurally mediated. The response closely paralleled changes in coronary flow, was mimicked by intracoronary injection of adenosine, and was reduced or absent if flow was already elevated by previous injection of adenosine. When BK eventually reached the systemic circulation, the resultant hypotension further reduced shortening in LAD region, with directionally similar effect in circumflex region. These results suggest that BK can increase regional shortening by enhancing coronary flow (Gregg phenomenon) as well as by altering global ventricular function through systemic hypotension. Such changes in shortening may contribute to stimulation of cardiac afferent nerves.
Are ground squirrels sleep deprived during hibernation?
Authors: Trachsel L. , Edgar D. M. , Heller H. C.
Published: December 2017

Hibernation is an adaptation for energy conservation, which probably evolved as an extension of non-rapid-eye-movement sleep mechanisms. Yet, during periodic arousals from bouts of deep hibernation, ground squirrels (Spermophilus lateralis) spend most of their time asleep. Spectral analysis of the electroencephalogram revealed that cortical slow-wave intensity during sleep is high at the beginning of a euthermic period and declines thereafter. Sleep slow-wave intensity is greater after longer bouts of hibernation than after shorter bouts. We hypothesize that low body temperatures during hibernation are incompatible with the restorative function of sleep as reflected in cortical slow-wave activity. Animals must incur the energetic costs of periodic arousals from hibernation to receive the restorative benefits of euthermic slow-wave sleep. The timing of arousals from hibernation may be a function of accumulated sleep debt.
Interactions between ANP and ANG II in regulating blood pressure and sympathetic outflow
Authors: Steele M. K. , Gardner D. G. , Xie P. L. , Schultz H. D.
Published: December 2017

In anesthetized rats with sinoaortic denervation, intracerebroventricular (icv) injection of atrial natriuretic peptide (ANP) resulted in decreased mean arterial blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (depressor effects), whereas icv angiotensin II (ANG II) produced increases in these variables (pressor effects). The depressor effects of ANP were slower in onset and longer in duration than the pressor effects of ANG II. Intracerebroventricular injection of the ANG II-receptor blocker sarthran or the ANG II-synthesis inhibitor captopril resulted in a significant reduction in MAP; HR and RSNA were not affected. Both sarthran and captopril abolished the depressor responses to icv ANP. In contrast, injection of an anti-rat ANP antibody, which blocked the depressor effects of icv ANP, did not by itself modify MAP, HR, or RSNA, nor did the antibody affect the pressor responses to icv ANG II. These data suggest that, in this animal model, the depressor effects of icv ANP are mediated by the inhibition of brain ANG II-dependent neural activity. These results also demonstrate that, in this preparation, the endogenous ANG II system actively contributes to the maintenance of basal MAP, whereas the central ANP system, at least in regions accessible to the antirat ANP antibody, plays little role in this maintenance.
Cardiac nerve blockade by infusion of procaine into the pericardial space of conscious dogs
Authors: O'Donnell C. P. , Scheuer D. A. , Keil L. C. , Thrasher T. N.
Published: December 2017

A technique was developed to produce acute, reversible cardiac nerve blockade (CNB) in the conscious dog by infusion of 2% procaine into the pericardial (PC) space. During CNB, reflex changes in heart rate (HR) in response to intravenous bolus injections of phenylephrine (100 micrograms) and nitroglycerin (300 micrograms) and the reflex tachycardia and hypotension after a 50-micrograms bolus injection of veratridine into the left atrium were abolished. In response to CNB, HR increased from 79 +/- 10 to 142 +/- 10 beats/min and mean arterial pressure (MAP) increased from 101 +/- 5 to 117 +/- 6 mmHg. Baseline values for plasma arginine vasopressin (AVP), plasma renin activity (PRA), and plasma norepinephrine (NE) were unchanged by CNB, but there was a small increase in plasma cortisol levels (1.4 +/- 0.3 to 2.3 +/- 0.3 micrograms/dl) during CNB. There was no significant change in the baseline levels of any of these hormones during PC infusion of 0.9% saline. To control for the possibility that procaine leaked into the systemic circulation, identical amounts of procaine were infused intravenously. Systemic administration of procaine caused a rise in MAP but had no effect on HR and did not alter plasma levels of AVP, PRA, NE, or cortisol. The relationship between plasma osmolality and plasma AVP, as well as the drinking response to a 60-min infusion of hypertonic NaCl, was unaltered by CNB. We conclude that PC procaine infusion is an effective technique for producing acute, reversible blockade of the cardiac nerves in the conscious dog.
Influence of angiotensin II on pressure natriuresis and renal hemodynamics in volume-expanded rats
Authors: Mattson D. L. , Raff H. , Roman R. J.
Published: December 2017

This study examined whether angiotensin II (ANG II) influences the pressure-natriuretic (PN) response by altering renal cortical or medullary hemodynamics. Studies were performed in Inactin-anesthetized rats that were acutely volume expanded to maintain plasma renin activity and ANG II levels in the physiological range. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of norepinephrine, vasopressin, cortisol, and aldosterone were fixed by intravenous infusion. In control rats (n = 8), sodium excretion increased from 3 to 17 microeq.min-1.g kidney wt-1 as renal perfusion pressure (RPP) was elevated from 96 to 141 mmHg (n = 8). Captopril (2 mg/kg, n = 9) reduced plasma levels of ANG II from 48 +/- 5 to 18 +/- 2 pg/ml, but it did not alter the PN relationship. Infusion of ANG II (20 ng.kg-1.min-1, n = 9) increased plasma levels of ANG II to 232 +/- 42 pg/ml and shifted the PN relationship to the right by 14 mmHg. Captopril increased renal blood flow, and infusion of ANG II returned it to control. Captopril had no effect on glomerular filtration rate (GFR) or glomerular capillary pressure (Pglom); however, subsequent ANG II infusion decreased Pglom from 56 +/- 2 to 48 +/- 2 mmHg and reduced GFR by 30%. Neither captopril nor ANG II altered papillary bloodflow or vasa recta capillary pressure at normal levels of RPP. These results indicate that the shift of the PN relationship during infusion of ANG II is due to a decrease in filtered load and enhanced tubular reabsorption of sodium. Acute blockade of the renin-angiotensin system had little effect on the PN response in volume-expanded rats despite affecting renal hemodynamics, because either the plasma and/or intrarenal levels of ANG II were already suppressed below those needed to influence tubular function or volume expansion inhibits tubular reabsorption in the nephron segments normally influenced by ANG II.
Excitatory pathways in smooth muscle investigated by phase-plot analysis of isometric force development
Authors: Van Koeveringe G. A. , Van Mastrigt R.
Published: December 2017

Excitatory pathways in the smooth muscle of the pig urinary bladder were investigated using phase-plot analysis of isometric contractions. The phase plots, plots of the rate of change of the force as a function of the force itself, were dominated by a straight line described by the horizontal intercept (Fiso) and the vertical intercept (U). The quotient Fiso/U is a time constant that characterizes the rate-limiting step in isometric force development in the muscle. Bladder strips of 1 mm diameter were activated by electrical field stimuli, acetylcholine, potassium, and ATP in combination with selective pathway inhibitors such as verapamil, atropine, or a calcium-free solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. When pathways that depended significantly on depolarization or intracellular calcium release were selected, the time constant was significantly smaller, indicating a faster process. The results indicated that the rate-limiting step in force development was determined by the influx of extracellular calcium.
Hepatic portal glucagon infusion decreases spontaneous meal size in rats
Authors: Le Sauter J. , Geary N.
Published: December 2017

We describe the first tests of intraportal pancreatic glucagon infusions during spontaneous meals in undisturbed, ad libitum-fed male Sprague-Dawley rats. Two-minute infusions beginning at meal onset and delivering 14 micrograms glucagon reduced the size and duration of both early and late nocturnal meals. After glucagon infusion during early nocturnal meals, neither the latency nor the size of the next meal was affected. Meal onset infusion of 3.4-14 micrograms glucagon/meal dose-dependently reduced late nocturnal meal size 19-64%. Full-meal glucagon infusions did not inhibit feeding more than 2-min infusions begun at meal onset or meal middle, despite fivefold differences in amount infused. These data indicate that spontaneous feeding is pharmacologically inhibited by prandial changes in hepatic portal glucagon concentration.
Evidence for metalloprotease involvement in the in vivo effects of big endothelin 1
Authors: Pollock D. M. , Opgenorth T. J.
Published: December 2017

The potent vasoconstrictor endothelin 1 (ET-1) is thought to arise from the proteolytic processing of big endothelin 1 (Big ET) by a unique endothelin-converting enzyme, possibly a metalloprotease. Experiments were conducted to determine the effects of Big ET on cardiovascular and renal functions during inhibition of metalloprotease activity in vivo. Intravenous infusion of Big ET (0.1 nmol.kg-1.min-1) in anesthetized euvolemic rats produced a significant increase in mean arterial pressure (MAP; 39 +/- 8%) and a decrease in effective renal plasma flow (ERPF; -39 +/- 2%), whereas glomerular filtration rate (GFR) remained unchanged (-8 +/- 8%). Simultaneous intravenous infusion of phosphoramidon (0.25 mg.kg-1.min-1), an inhibitor of metalloprotease activity including neutral endopeptidase EC 3.4.24.11 (NEP), completely prevented these effects of Big ET. Thiorphan (0.1 mg.kg-1.min-1), also an inhibitor of NEP, had absolutely no effect on either the renal or cardiovascular response to Big ET. Similarly, the response to Big ET was unaffected by infusion of enalaprilat (0.1 mg.kg-1.min-1), an inhibitor of the angiotensin-converting enzyme, which is also a metalloprotease. To determine whether the effect of phosphoramidon was due to antagonism of ET-1, an identical series of experiments was performed using ET-1 infusion (0.02 nmol.kg-1.min-1). Although the increase in MAP (24 +/- 5%) produced by ET-1 was less than that observed for the given dose of Big ET, the renal vasoconstriction was much more severe; the smaller peptide changed ERPF and GFR by -66 +/- 7 and -54 +/- 9%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Neurons in rabbit caudal ventrolateral medulla inhibit bulbospinal barosensitive neurons in rostral medulla
Authors: Li Y. W. , Gieroba Z. J. , McAllen R. M. , Blessing W. W.
Published: December 2017

We made extracellular recordings from 104 spinally projecting neurons in the rostral ventrolateral medulla of urethan-anesthetized rabbits to test whether inhibitory vasomotor neurons in the caudal ventrolateral medulla act by inhibiting rostral sympathoexcitatory neurons. The median conduction velocity was 8.3 m/s, and the median discharge rate was 2.9 spikes/s. Raising arterial pressure with intravenous phenylephrine inhibited 88% of 77 neurons tested. The remaining units were excited. Lowering arterial pressure with nitroprusside excited 90% of 30 neurons tested. Remaining units were unaffected. Ninety-one percent of 58 rostral neurons inhibited by phenylephrine were also inhibited by injection of L-glutamate into the caudal ventrolateral medulla and 81% of 43 tested were excited by caudal injection of gamma-aminobutyric acid. These results confirm our suggestion [Brain Res. 253: 161-171, 1982; Am. J. Physiol. 254 (Heart Circ. Physiol. 23): H686-H692, 1988] and the findings of S. K. Agarwal, A. J. Gelsema, and F. R. Calaresu [Am. J. Physiol. 257 (Regulatory Integrative Comp. Physiol. 26): R265-R270, 1989]. The depressor neurons in the caudal medulla act substantially by inhibition of spinally projecting sympathoexcitatory neurons in the rostral medulla. All rostral units excited by phenylephrine were also excited by injections of L-glutamate into the caudal ventrolateral medulla, suggesting that some sympathoinhibition of baroreceptor and caudal medullary origin may take place in the spinal cord and be mediated by a subpopulation of rostral sympathoinhibitory neurons.
Naltrexone, an opioid blocker, alters taste perception and nutrient intake in humans
Authors: Bertino M. , Beauchamp G. K. , Engelman K.
Published: December 2017

To test the hypothesis that reduced food intake produced by opioid blockade is due to a reduction in the pleasant aspects of tastes, 18 fasted male college students rated the intensity and pleasantness of soup that contained various concentrations of NaCl and of Kool-Aid that contained various concentrations of sucrose at hourly intervals after ingesting either naltrexone (50 mg) or a placebo in a double-blind study. Hunger, fullness, nausea, and current mood state were also assessed. Lunch followed and food intake was recorded. After placebo, the pleasantness of the salted soup increased as lunchtime approached. After naltrexone, however, soup pleasantness remained unchanged across time. Similar changes were obtained for perceived sweetness and pleasantness of Kool-Aid and for the perceived saltiness of soup. Naltrexone also blocked the increases in hunger ratings that occurred across time in the placebo condition. Nausea was higher after naltrexone. After naltrexone, subjects consumed approximately 500 kcal less at lunch than after placebo. Analysis of covariance suggested that decreased hunger (but not nausea or taste pleasantness) accounted for the naltrexone-induced reduction of food intake.
Interactions between brain acetylcholine and prostaglandins in control of vasopressin release
Authors: Inoue M. , Crofton J. T. , Share L.
Published: December 2017

We have examined in conscious rats the interaction between centrally acting prostanoids and acetylcholine in the stimulation of vasopressin secretion. The intracerebroventricular (icv) administration of carbachol (25 ng) resulted in marked transient increases in the plasma vasopressin concentration and mean arterial blood pressure and a transient reduction in heart rate. Central cyclooxygenase blockade by pretreatment icv with either meclofenamate (100 micrograms) or indomethacin (100 micrograms) virtually completely blocked these responses. Prostaglandin (PG) D2 (20 micrograms icv) caused transient increases in the plasma vasopressin concentration (much smaller than after carbachol) and heart rate, whereas mean arterial blood pressure rose gradually during the 15-min course of the experiment. Pretreatment with the muscarinic antagonist atropine (10 micrograms icv) decreased the peak vasopressin response to icv PGD2 by approximately one-third but had no effect on the cardiovascular responses. We conclude that the stimulation of vasopressin release by centrally acting acetylcholine is dependent on increased prostanoid biosynthesis. On the other hand, stimulation of vasopressin release by icv PGD2 is partially dependent on activation of a cholinergic pathway.
Comparison between effects of interleukin-1 alpha administration and sublethal endotoxemia in primates
Authors: Fischer E. , Marano M. A. , Barber A. E. , Hudson A. , Lee K. , Rock C. S. , Hawes A. S. , Thompson R. C. , Hayes T. J. , Anderson T. D. , et al.
Published: December 2017

Interleukin (IL)-1 is an early mediator of host response to inflammation, although its contribution to individual components of the acute phase reaction is still unclear. To evaluate how the hemodynamic, metabolic, and hormonal responses to sublethal endotoxemia compare with IL-1 administration, baboons received intravenously either lipopolysaccharide (LPS) or 0.1, 10, or 100 micrograms/kg IL-1 alpha. LPS induced an early tachycardia and a fall in mean arterial pressure, as well as lacticacidemia and hypoaminoacidemia. Similar hemodynamic and metabolic changes were seen with 10 or 100 micrograms/kg of IL-1 alpha. An increase in adrenocorticotropic hormone and fall in serum iron were induced by IL-1 alpha but not by LPS. Plasma tumor necrosis factor-alpha (TNF-alpha) was not measurable after IL-1 alpha administration, whereas LPS induced a monophasic TNF-alpha response. IL-6 levels were significantly greater after LPS than IL-1 alpha administration. Histopathological lesions, similar in LPS- and 100 micrograms/kg IL-1 alpha-treated groups, were present only in the adrenal cortex. We conclude that many, but not all, of the effects of sublethal endotoxemia can be replicated by IL-1 alpha administration, and these responses are dose dependent.
Phase response curves to light in young and old hamsters
Authors: Rosenberg R. S. , Zee P. C. , Turek F. W.
Published: December 2017

The phase-shifting effects of 1-h light pulses on the circadian rhythm of locomotor activity were measured in young (less than 12 mo old) and old (greater than 16 mo old) hamsters. Phase response curves (PRCs) for both age groups showed an inactive region [approximately circadian time (CT) 0 through CT12], a delay region (CT12 through CT16), and an advance region (CT16 through CT24) as has been reported for young animals. Significant age group differences in the amplitude of phase shifts were measured, with older animals showing larger shifts limited to the region of the "break point" at CT16. The free-running period of the activity rhythm was measured before the first light pulse; age-related decreases of period length consistent with previous reports were measured. The findings indicate that the response of the circadian clock to the major environmental synchronizing agent, light, is different in old hamsters compared with young adults.
Characterization of electroencephalographic state in fetal baboons
Authors: Stark R. I. , Haiken J. , Nordli D. , Myers M. M.
Published: December 2017

Long-term recordings of the electroencephalograms (EEGs) from the non-human fetal primate have been visually scored for state. Data were obtained from three fetuses using recently developed techniques for chronic instrumentation of the pregnant baboon. Seven days or more after surgery, nine chart records of 4-5 h in duration were analyzed. These records were made during an interval in gestation from 143 to 153 days (term = 175 to 185 days). Criteria for differentiation of EEG state were based on the presence (state 1) or absence (state 2) of trace alternant, which is the predominant characteristic of EEG activity during quiet sleep in human preterm and term infants. Two patterns of EEG activity were readily distinguished at both standard (30 mm/s) and compressed (30 mm/min) EEG chart speeds. On a minute-by-minute basis, there was an overall concurrence of 82.9% for EEG state when scored from compressed and standard EEG records. From the compressed records, state 1 was present on average 38.3% of the time, with a mean epoch duration of 15.1 min, while epochs of state 2 averaged 25.9 min. We conclude that at least two EEG states are present at this gestation in the fetal baboon. These two states can be reliably defined visually by scoring methods directly comparable to those used for EEG recognition of sleep states in the human newborn infant. To validate the conclusion that these fetal state assignments based on patterns of EEG activity correspond to sleep states, it will be necessary to determine if the oscillations of other physiological parameters are coherent with these patterns.
Thermoregulation, growth, and reproduction in Alaskan collared lemmings: role of short day and cold
Authors: Maier H. A. , Feist D. D.
Published: December 2017

To assess factors controlling seasonal thermoregulatory and reproductive changes, collared lemmings (Dicrostonyx groenlandicus) were exposed for 16 wk to long day (LD, 22 h light: 2 h dark) and warm (15 +/- 3 degrees C), LD and cold (1 +/- 0.5 degrees C), short day (SD, 4 h light: 20 h dark) and warm, SD and cold or acclimatized to outdoor winter conditions (OUT). Hair length and color, body mass, and food intake were monitored weekly. Resting metabolic rates (RMR) and nonshivering thermogenesis (NST) were estimated several times by measuring oxygen consumption before and after norepinephrine injections. Body composition and reproductive condition were determined at the end of the experiment. SD and OUT groups had a 15.8% lower (P less than 0.01) RMR at 7 degrees C than the LD groups. Lower thermal conductance in SD and OUT animals appears due to molt to white winter pelage, which occurred by week 3 in SD but not in LD groups. Neither SD, cold, nor OUT altered NST or reproductive morphology. SD-exposed lemmings showed 19.2% greater growth than those in LD, resulting primarily from a 29.2 and 15.0% increase in lean and ash components, respectively. Cold exposure increased food intake by 34.7%. Results suggest that the pineal gland, which mediates SD effects, may influence molt and growth but not NST or reproductive morphology.
Role of circulation in maintaining Na+ and K+ concentration in pelvic patch in Rana catesbeiana
Authors: Parsons R. H. , Schwartz R.
Published: December 2017

Skin samples from the pelvic, pectoral, and back areas of frogs were taken from control (C) animals and from dehydrated animals under three conditions: dehydrated and not exposed to a bathing medium (D), dehydrated live and ventral surface exposed to a bathing medium (DL), and dehydrated with heart stopped and ventral surface exposed to a bathing medium (DHS). The skin concentration of Na+ and K+ of the pelvic patch in the absence of circulation was significantly reduced [DHS 286 +/- 22 microM/mg dry wt (n = 6)] compared with control [C 392 +/- 21 microM/mg dry wt (n = 8)]. However, the pelvic skin concentration was maintained in a frog with an intact circulation [DL 381 +/- 26 microM/mg dry wt (n = 7)] even in the presence of a high pelvic water flow [684 +/- 105 cm3.cm-2.s-1.10(-7) (n = 13)]. The water uptake in the pectoral region [231 +/- 54 cm3.cm-2.s-1.10(-7) (n = 13)] was not high enough to predict a dilution, and none was found. The concentrations were 354 +/- 21 (n = 8), 359 +/- 22 (n = 7), 353 +/- 26 (n = 7), and 373 +/- 45 microM/mg dry wt (n = 6) for C, D, DL, and DHS, respectively. Examination of the Na+ and K+ concentrations separately in the pelvic skin shows that the lower salt content in DHS frogs is mainly due to a loss of Na+.(ABSTRACT TRUNCATED AT 250 WORDS)