bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of in situ canine intrinsic cardiac neuronal activity by nicotinic, muscarinic, and beta-adrenergic agonists
Authors: Huang M. H. , Smith F. M. , Armour J. A.
Published: December 2017

To investigate whether microvolumes (< or = 10 microliters) of nicotinic, muscarinic, and beta-adrenergic agonists can modify intrinsic cardiac neuronal activity, nicotine, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), bethanechol chloride, and isoproterenol were separately administered adjacent to spontaneously active in situ epicardial neurons in 15 anesthetized dogs. Neuronal activity generated by 46 of 63 neurons was modified by these neurochemicals, with about half of the neurons affected by more than one agent. In association with these neuronal responses, cardiodynamic responses were elicited in 17 instances. When cardiac augmentation was elicited, it persisted after the administration of atropine but not of timolol. After cardiac decentralization, 40% of previously active neurons were still modified by local application of chemicals; cardiodynamic responses were elicited in nine instances. The activity of six units was modified by isoproterenol after subsequent administration of hexamethonium. These data confirm that intrinsic cardiac neurons possess nicotinic and muscarinic receptors and demonstrate that some intrinsic cardiac neurons also possess beta-adrenergic receptors. Furthermore, these data demonstrate that intrinsic cardiac neurons with nicotinic, muscarinic, and beta-adrenergic receptors are involved in cardiac regulation.
Effect of superhypercapnia on cortical pHi and cortical blood flow
Authors: Tomlinson F. H. , Anderson R. E. , Meyer F. B.
Published: December 2017

In vivo panoramic imaging of regional cortical blood flow and intracellular brain pH with umbelliferone fluorescence was performed in fasted New Zealand White rabbits (n = 30) subjected to constant or stepwise increases in arterial PCO2 (PaCO2) up to 160 mmHg under 1.0% halothane anesthesia. At a PaCO2 of 40 mmHg, baseline brain pHi measured 7.03 +/- 0.04, while regional cortical blood flow was 47.0 +/- 4.3 ml.100 g-1.min-1. With an immediate but constant exposure to a PaCO2 of 60, 80, or 120 mmHg, at 15 min pHi fell to 6.94 +/- 0.03, 6.89 +/- 0.03, and 6.90 +/- 0.03 and recovered over 20, 80, and 120 min, respectively. At 160 mmHg PaCO2, pHi fell to 6.68 +/- 0.04 and remained acidotic. With stepwise increases in PaCO2 up to 80 mmHg, brain pHi decreased from 7.01 +/- 0.02 to 6.99 +/- 0.02, not significantly different despite a severe systemic acidosis of 7.022 +/- 0.034. At a PaCO2 of 120 and 160 mmHg, pHi dropped to 6.97 +/- 0.02 and 6.93 +/- 0.02, respectively. The difference in brain pHi between an immediate and stepwise exposure to a PaCO2 of 160 mmHg was significant (P < 0.005). These results demonstrate that brain pHi is tightly regulated across the cortical surface and resistant to profound changes in extracellular pH. The difference in pHi between the constant and incremental increases in PaCO2 suggests that there is upregulation of pH homeostatic mechanisms.
Cerebral metabolism and electrocortical activity in the chronically hyperglycemic lamb
Authors: Rosenkrantz T. S. , Knox I. , Zalneraitis E. L. , Raye J. R. , Porte P. J. , Cramer R. , Smoloski R. , Philipps A. F.
Published: December 2017

Pages R1262–R1269: T. S. Rosenkrantz, I. Knox, E. L. Zalneraitis, J. R. Raye, P. J. Porte, R. Cramer, R. Smoloski, and A. F. Philipps. “Cerebral metabolism and electrocortical activity in the chronically hyperglycemic lamb.” Page R1265: Several errors relating to significance of changes in arterial oxygen concentration, cerebral oxygen delivery, and cerebral oxygen uptake were introduced into Table 1 by the publisher. All of the information in the abstract and text are correct as originally printed. A corrected version of the table is reprinted below. Note that there were no changes in the fetal arterial oxygen content during any of the study periods, cerebral oxygen delivery rose during G2 (P = 0.06), and there was a significant increase in cerebral oxygen uptake during G2 (P < 0.05). It is hoped that this clarifies conflicting information in the text and the table concerning the metabolic changes that occur in the brain of the chronically hyperglycemic fetal lamb.

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Calcium channel antagonists prevent urinary bladder growth and neuroplasticity following mechanical stress
Authors: Steers W. D. , Albo M. , Tuttle J. B.
Published: December 2017

Cytosolic Ca2+ has been postulated to regulate smooth muscle hypertrophy and growth factor production. Consistent with this hypothesis we report that the Ca2+ channel antagonists verapamil and diltiazem prevent bladder and neuronal growth in rats in response to 3 wk of urethral obstruction. Ca2+ channel blockers prevented 30-45% of the increase in bladder weight, protein, and DNA content found in obstructed animals. Similarly, these drugs produced a 15-27% reduction in area profiles for retrogradely labeled (Fluoro-Gold) motoneurons in the major pelvic ganglia and afferents in the L6-S1 dorsal root ganglia after obstruction. The reduced growth in neuronal areas was attributed, in part, to less nerve growth factor (NGF) in bladders of obstructed rats receiving verapamil (8.5 pg/bladder) or diltiazem (14.5 pg/bladder) compared with obstructed animals not given these drugs (58.2 pg/bladder). The alpha 1-adrenergic antagonist, prazosin, while decreasing voiding frequency in obstructed rats, had no significant impact on bladder weight or neuronal size. These reductions in the increase in bladder hypertrophy and NGF content may be due to altered handling of Ca2+.
Atrial natriuretic peptide and glomerular hyperfiltration during onset of spontaneous diabetes mellitus
Authors: Okwueze M. I. , Opgenorth T. J. , von Geldern T. W. , Vari R. C.
Published: December 2017

The mechanisms responsible for the elevation of glomerular filtration rate (GFR) in early stages of insulin-dependent diabetes mellitus (IDDM) are undefined. The objectives of this study were to define the temporal pattern of onset of glomerular hyperfiltration in the spontaneously diabetes-prone (BB/DP) rat and to evaluate the possible role of atrial natriuretic peptide (ANP) as the primary mediator of the observed alterations in renal hemodynamics. GFR was significantly higher (1.38 +/- 0.07 ml.min-1 x g-1; n = 5) in moderately hyperglycemic BB/DP rats (blood glucose > 270 mg/dl) 14 days after the onset of IDDM compared with age-matched diabetes-resistant rats (BB/DR), which averaged 1.03 +/- 0.07 ml.min-1 x g-1 (n = 7). Circulating ANP levels in moderately hyperglycemic BB/DP rats 1, 7, and 14 days after onset of IDDM were within the normal range, averaging 100 +/- 21, 57 +/- 12, and 65 +/- 6 pg/ml, respectively, and were not significantly different (P > 0.05) from ANP levels in age-matched normoglycemic BB/DR rats. To further test the role of ANP in glomerular hyperfiltration, an ANP receptor antagonist was infused into anesthetized BB/DP rats (n = 10) 14 days after onset of IDDM, after baseline measurements of mean arterial pressure, renal hemodynamics, and renal fluid and electrolyte excretions. ANP receptor antagonism caused a significant reduction in mean arterial pressure from 120 +/- 3 to 103 +/- 2 mmHg; however, there were no significant effects of ANP receptor blockade on GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of acute hypoxia on phosphate excretion in rats
Authors: Mimura Y. , Knox F. G.
Published: December 2017

This study evaluated the effect of acute hypoxia on renal handling of phosphate in rats in the presence and absence of parathyroid hormone (PTH). Hypoxia causes respiratory alkalosis in spontaneously breathing humans and animals. Respiratory alkalosis has been reported to induce a blunted phosphaturic response to PTH. In this study, to avoid the confounding effect of hypocapnia accompanying the hypoxia on phosphate excretion, the rats were ventilated mechanically, and arterial PCO2 levels were controlled. Rats were divided into two main groups depending on the arterial PO2 levels: a hypoxic group (n = 16) and a normoxic group (n = 18). Hypoxia was produced by ventilating with 10% oxygen, and hypocapnia was produced by hyperventilation. In response to PTH, the hypoxic rats without hypocapnia showed a greater increase in fractional excretion of phosphate (FEPi; 37.7 +/- 2.6%, mean +/- SE) compared with normoxic rats (27.4 +/- 2.5%, P < 0.02). During hypocapnia, there was no difference in FEPi between hypoxic and normoxic groups (21.2 +/- 1.5 and 19.5 +/- 1.2%, respectively), and both groups showed a significantly blunted phosphaturic response to PTH compared with normocapnia (P < 0.05 and P < 0.01, respectively). Urinary adenosine 3',5'-cyclic monophosphate (cAMP) increased similarly after PTH infusion between each group. To test whether the phosphaturic effect of PTH in hypoxia and the blunted phosphaturic effect of PTH in hypocapnia are due to steps beyond the generation of cAMP, the phosphaturic response to cAMP infusion was evaluated in 1) hypoxic and normocapnic rats (n = 6), 2) normoxic and normocapnic (control) rats (n = 6), and 3) normoxic and hypocapnic rats (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic stimulated skeletal muscle glycogenolysis in perfused hindlimbs of young and old male Fischer 344 rats
Authors: Larkin L. M. , Horwitz B. A. , Eiffert K. C. , McDonald R. B.
Published: December 2017

Epinephrine (Epi)- and forskolin (FSK)-stimulated glycogenolysis of skeletal muscle was evaluated in perfused hindlimb isolated from male Fischer 344 (F344) rats, ages 6, 12, and 26 mo. Muscle glycogen stores were reduced by sciatic nerve stimulation and replenished by infusing 10 mM glucose, 500 microU insulin, and 5 microCi [14C]glucose via a left carotid artery cannula. Then the hindlimb was perfused with a modified Krebs-Henseleit buffer (pH 7.4). At minute 20 of the perfusion, Epi [0.0 (perfusate), 0.25, 0.50, or 0.75 microM] or 40 microM FSK were infused for 10 min. Radioactivity (14C) in the effluent perfusate was collected every 60 s during a 20-min preinfusion, a 10-min Epi infusion, and a 20-min postinfusion period and was used to determine the rate of muscle glycogen utilization. Total 14C release increased with Epi and 40 microM FSK. However, the pattern of release did not differ significantly with age. In general, the fraction of the perfusate released as 14CO2 increased in the presence of FSK and Epi but did not significantly differ with age. [14C]lactate released in response to Epi increased in the 6-mo-old group, remained unchanged in the 12-mo-old group, and decreased in the 26-mo-old group compared with 0.0 Epi (perfusate) values. It appears that stimulation of skeletal muscle glycogenolysis via adrenergic receptor or postreceptor/adenosine 3',5'-cyclic monophosphate-mediated mechanisms is unaffected by age. However, the utilization of carbohydrate by isolated hindlimb muscle is altered in the aging rat, resulting in a more oxidative metabolism.
Effect of ethanol on immature ovine fetal breathing movements, fetal prostaglandin E2, and myometrial activity
Authors: Bocking A. D. , Carmichael L. J. , Abdollah S. , Sinervo K. R. , Smith G. N. , Brien J. F.
Published: December 2017

In the mature ovine fetus, ethanol decreases fetal breathing movements (FBM), which is temporally related to increased prostaglandin E2 (PGE2) concentration, decreases blood glucose concentration, increases blood lactate concentration, and decreases uterine electromyographic (EMG) activity. The objective of this study was to determine the effects of ethanol on these variables in the immature fetal sheep. Experiments were conducted in pregnant ewes at 85-94 days of gestation (full term 147 days) that received a 1-h maternal infusion of 1 g ethanol/kg maternal body wt (n = 9) or an equivalent volume of saline (n = 5). The maximal maternal and fetal blood ethanol concentrations for the ethanol regimen were 1.305 +/- 0.165 and 1.458 +/- 0.137 mg/ml, respectively. Maternal infusion of ethanol (or saline) did not change the incidence of FBM, fetal plasma PGE2 concentration, heart rate, blood pressure, blood gases and pH, or uterine EMG activity. Ethanol decreased (P < 0.05) fetal blood glucose concentration from 1.18 +/- 0.10 to 0.87 +/- 0.07 and 0.89 +/- 0.09 mM at 1 and 3 h, respectively, but did not alter blood lactate concentration compared with saline infusion. These data support the hypothesis that the effects of ethanol on FBM, fetal plasma PGE2 and blood lactate concentrations, and uterine EMG activity are gestational age dependent.
Sodium appetite, thirst, and body fluid regulation in humans during rehydration without sodium replacement
Authors: Takamata A. , Mack G. W. , Gillen C. M. , Nadel E. R.
Published: December 2017

After a 7-h H2O and Na+ depletion period (DP), produced by intermittent light exercise (8 bouts) at 35 degrees C, we examined thirst and taste palatability responses to 10 different NaCl solutions during 23 h of rehydration (RH) at 25 degrees C. During DP, net H2O and Na+ loss were 27.2 +/- 2.9 ml/kg and 3.29 +/- 0.45 meq/kg, respectively. Plasma osmolality (POsm) and plasma Na+ concentration ([Na+]p) increased significantly during DP by 3.4 +/- 1.2 mosmol/kgH2O and 3.0 +/- 1.0 meq/kgH2O, respectively. Plasma volume (PV) decreased by 6.5 +/- 1.9%. Thirst rating, renal fractional reabsorption of H2O, and plasma arginine vasopressin concentration (PAVP) increased as POsm increased. This increased thirst was accompanied by increased palatability ratings to H2O. During RH, subjects drank deionized H2O ad libitum and ate a Na(+)-free diet for 23 h. POsm and [Na+]p returned to control levels within 1 h RH and remained at or below the control thereafter. PV remained reduced by approximately 5% throughout RH. The increased thirst and PAVP returned to their respective control levels within 1 h of RH as POsm decreased, but thirst rating increased against between 17 and 23 h of RH without increase in POsm or PAVP. Palatability ratings to a 1 M NaCl solution at and after 3 h RH and palatability ratings to 0.3 M at 17 and 23 h RH were significantly higher than control. Plasma aldosterone concentration (PAldo) increased after DP, decreased with drinking, and increased again between 6 and 23 h of RH, accompanied by a marked decrease in fractional Na+ excretion to < 0.07%. Thus both Na+ preference and thirst in humans are influenced by body fluid and electrolyte status. The increased Na+ palatability (Na+ appetite) was preceded by osmotically induced thirst, and accompanied by nonosmotically driven thirst [extracellular fluid (ECF) thirst] and increased PAldo. The "Na+ appetite" and "ECF thirst" along with increased renal Na+ retention could contribute to ECF volume regulation after thermally induced H2O and Na+ depletion.
Acute hypocapnia blunts natriuretic and diuretic effects of atrial natriuretic factor in rats
Authors: Mimura Y. , Khraibi A. A. , Heublein D. M. , Knox F. G.
Published: December 2017

Recent studies suggest that the autonomic nervous system, when activated by respiratory alkalosis, may attenuate the renal effects of atrial natriuretic factor (ANF). We evaluated the renal responses to infusion of ANF during acute exposure to hypocapnia in the presence or absence of the renal nerves in anesthetized rats. In this study, renal function during hypocapnia was assessed and was compared with renal function during normocapnia produced by normal ventilation as well as by hyperventilation. Rats were divided into three experimental groups (n = 8): 1) a normally ventilated normocapnic (NV-N) (control) group; 2) a hyperventilated normocapnic (HV-N) group; and 3) a hyperventilated hypocapnic (HV-H) group. The innervated (Inn) right kidney served as a control for the contralateral denervated (DNX) kidney. In Inn and DNX kidneys of HV-H rats, an infusion of ANF (12 micrograms.kg-1.h-1) produced a smaller increase in urine flow rate (delta V: 9.8 +/- 3.9 and 1.3 +/- 4.2 microliters/min) and in fractional Na excretion (delta FENa: 1.35 +/- 0.52 and 0.73 +/- 0.58%) compared with NV-N rats (delta V: 37.6 +/- 4.9 and 59.9 +/- 9.7 microliters/min; delta FENa: 3.24 +/- 0.37 and 3.88 +/- 0.65%). No differences were observed in delta V and delta FENa in Inn kidney between HV-H and HV-N groups; however, the attenuated natriuretic and diuretic responses to ANF in DNX kidney of HV-H rats were also observed in comparison with HV-N rats (delta V: 27.4 +/- 4.3 microliters/min; delta FENa: 2.94 +/- 0.48%). ANF induced natriuresis in DNX kidney to the same degree in NV-N and HV-N rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Exogenous arginine vasopressin does not enhance carotid baroreflex control in the conscious dog
Authors: Wolfer R. S. , Lovell N. H. , Brunner M. J.
Published: December 2017

Arginine vasopressin (AVP) has profound effects on the cardiovascular system, yet has minimal pressor activity at physiological levels in intact subjects. We designed an investigation to delineate the effects of AVP on open-loop carotid baroreflex control of mean arterial pressure (MAP), total peripheral resistance (TPR), and cardiac output (CO) in conscious, chronically instrumented dogs. During graded infusions of AVP (0.5-2.0 ng.kg-1.min-1), the open-loop hemodynamic responses to controlled changes in isolated carotid sinus pressure (CSP) were determined. Increasing levels of AVP infusion led to significant increases in plasma AVP levels (P < 0.01). Increasing doses of AVP led to significant increases in TPR at all levels of CSP (P < 0.01). The overall range and gain of the response were not significantly different at any level of AVP infusion. Despite this increase in systemic resistance, there was no significant change in the MAP-CSP relationship. Infusion of AVP led to a dose-dependent depression in CO (P < 0.01) and heart rate (HR; P < 0.05) at all levels of CSP with no significant effect on open-loop baroreflex control. We conclude that although exogenous AVP induces profound changes in cardiovascular function, it does not alter carotid baroreflex control of MAP, TPR, CO, and HR.
An X-ray microanalysis study of Locusta Malpighian tubule cell function using rubidium
Authors: Pivovarova N. , Marshall S. L. , Anstee J. H. , Bowler K.
Published: December 2017

Intracellular distributions of Na, K, Mg, Ca, Cl, P, and S were determined in type 1 Malpighian tubule cells of Locusta using X-ray microanalysis. K showed a gradient of increasing concentration from basal to apical surfaces. No other element showed this distribution. Na was below the detection limit. Three types of dark body were present in cytoplasm; one rich in Ca and P and two rich in K and P. Incubation in Rb-Ringer solution resulted in a dramatic fall in cellular K that was not completely replaced by Rb. The distribution of Rb mimicked that of K. Na levels were significantly increased, but the total intracellular monovalent metal concentration was less than in controls. Other elements were little affected. Rb replaced K in dark bodies. Tubules continued to secrete K-rich urine in Rb-Ringer solution even though intracellular [K] was low. Little Rb+ was secreted and Na+ secretion was unchanged. The possible role of dark bodies as a source of secreted K+ is discussed.
Effect of hepatic portal infusion of pyruvate on pancreatic hormone response during exercise
Authors: Cardin S. , Helie R. , Bergeron R. , Comte B. , van de Werve G. , Lavoie J. M.
Published: December 2017

The purpose of the present investigation was to evaluate the effects of a small infusion of pyruvate into the hepatic portal vein on the pancreatic hormone response during exercise (30-min treadmill run; 26 m/min, 0% grade) in adrenodemedullated rats. Resting and exercising rats were infused with either pyruvate (5% solution; 0.016 ml/min) into the portal vein, pyruvate into the jugular vein, or saline into the portal vein. Peripheral and portal blood glucose concentrations were decreased (P < 0.01) similarly in all groups after the exercise period. Peripheral insulin, glucagon, and norepinephrine levels, either at rest or after exercise, were not significantly affected by the infusions. The response of portal pancreatic hormone concentrations to exercise was, however, reduced by the pyruvate infused into the portal and jugular veins for insulin and into the portal vein only for glucagon. The normal increase in peripheral glucagon-insulin molar ratio during exercise was shut down by the infusion of pyruvate into the portal vein but not by the infusion of pyruvate into the jugular vein or by the infusion of saline. These results indicate that a small blood infusion of pyruvate, even in the presence of a decreasing blood glucose level, can attenuate substantially the pancreatic hormone response during exercise in adrenodemedullated rats.
Involvement of liver and skeletal muscle in sucrose-induced insulin resistance: dose-response studies
Authors: Pagliassotti M. J. , Shahrokhi K. A. , Moscarello M.
Published: December 2017

The ability of dietary sucrose to induce insulin resistance independent of changes in body weight is controversial. In the present study male rats were fed a high-starch (ST) diet (starch 68% of total kcal) ad libitum for 2 wk and then were fed equicalorically either the ST diet or a high-sucrose (SU) diet (sucrose 68% of total kcal) for 8 wk. Euglycemic, hyperinsulinemic (0, 1.2, 4.1, 8, 15 mU.kg-1.min-1, n = 6-8/group per dose) clamps were then used to establish dose-response relationships for glucose kinetics and metabolism. Body weight (513 +/- 3 g) and composition were similar between groups after the 8-wk dietary period. Glucose infusion rates (GIR; mg.kg-1.min-1) were significantly less in SU (0.9 +/- 5.8 +/- 0.6, 14.8 +/- 1.3, and 18 +/- 1.1) than in ST rats (4.1 +/- 0.9, 12.3 +/- 1.2, 22.6 +/- 1.5, and 25.9 +/- 1.8) at 1.2, 4.1, 8, and 15 mU.kg-1.min-1, respectively. Impaired suppression of endogenous glucose production accounted for 46, 43, 23, and 0% of the reduction in GIR in SU rats at 1.2, 4.1, 8, and 15 mU.kg-1.min-1, respectively. Despite basal hyperinsulinemia (38 +/- 2 microU/ml in SU vs. 26 +/- 2 microU/ml in ST rats), liver phosphoenolpyruvate carboxykinase (PEPCK) activity was 50% higher in SU than in ST rats and remained elevated in SU rats (by 30-40%) at the two lower insulin doses. No skeletal muscle glycogen accumulation occurred in SU rats at any of the insulin doses, and glycogen synthase I activity was significantly lower in SU rats at the two highest insulin doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of surgery on the pituitary-adrenal response to repeated hemorrhage
Authors: Lilly M. P.
Published: December 2017

We studied the effect of surgery on hemorrhage-induced facilitation in the pituitary-adrenal system using repeated hemorrhage in chronically prepared dogs. Animals underwent splenectomy and adrenal venous and femoral arterial catheterization. Two (day 2) or five (day 5) days later, animals were anesthetized with pentobarbital, respired, and subjected to two periods of hypovolemia (20% hemorrhage with reinfusion of shed blood at 30 min; H1 and H2) separated by 90 min. Arterial and adrenal venous blood was sampled, and adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), angiotensin II (ANG II), cortisol, and cortisol secretion were measured. On day 2, cortisol secretion increased similarly after H1 and H2, despite a smaller response of ACTH to H2. On day 5, neither ACTH nor cortisol secretion changed after H1, but both increased significantly after H2. The adrenal sensitivity to ACTH increased after H2 on day 2 and was similar after H2 on both days. AVP and ANG II increased similarly after H1 and H2 on each day but had larger responses on day 2. These results suggest 1) either surgery or initial hemorrhage can lead to enhanced pituitary-adrenal responses to subsequent hemorrhage, 2) this effect may have both central and adrenal components, 3) negative feedback may inhibit enhanced responses of ACTH in this model, 4) changes in adrenal sensitivity to ACTH may not depend on an initial pituitary-adrenal response and may not be blocked by increased circulating corticosteroids, and 5) differences in circulating AVP or ANG II do not account for facilitation in pituitary-adrenal responses.
Effect of postgastric energy loads on intake of sham meals of different palatability in rats
Authors: Rigaud D. , Betoulle D. , Chauvel A. , Alberto L. A. , Apfelbaum M.
Published: December 2017

Food intake depends on the palatability of the diet and on the energy delivered to the body. It is not known, however, whether the palatability of a diet is able to modulate the inhibitory effect of energy input on food intake. To address this question, we have measured intake during sham feeding for diets of different palatabilities in rats receiving varying levels of duodenal energy load. Rats were offered sucrose solutions (6, 10, or 30%) or mixed liquid diets without or with physiological duodenal energy loads using a mixed liquid diet. Compared with that seen during real feeding, meal size during sham feeding was increased for palatable diets but not for less palatable diets. Intraduodenal infusion of the mixed liquid diet inhibited the intake of all diets given by sham feeding. This inhibition was dependent on the level of duodenal energy load and was significantly greater for more palatable diets than for less palatable ones. We conclude that the inhibitory effects of intestinal nutrient load on intake are significant for all diets but have a more pronounced effect on the intake of highly palatable diets.
Direct measurement of renal medullary blood flow in the dog
Authors: Strick D. M. , Fiksen-Olsen M. J. , Lockhart J. C. , Roman R. J. , Romero J. C.
Published: December 2017

We studied the responses of total renal blood flow (RBF) and renal medullary blood flow (RMBF) to changes in renal perfusion pressure (RPP) within and below the range of renal autoregulation in the anesthetized dog (n = 7). To measure RMBF, we developed a technique in which the medulla is exposed by excising a section of infarcted cortex and a multiple optical fiber flow probe, connected to a laser-Doppler flowmeter, is placed on the medulla. At the baseline RPP of 120 +/- 1 mmHg, RBF was 2.58 +/- 0.33 ml.min-1.g perfused kidney wt-1, and RMBF was 222 +/- 45 perfusion units. RPP was then decreased in consecutive 20-mmHg steps to 39 +/- 1 mmHg. At 80 +/- 1 mmHg, RBF remained at 89 +/- 4% of the baseline value; however, RMBF had decreased significantly (P < 0.05) to 73 +/- 4% of its baseline value. The efficiency of autoregulation of RBF and of RMBF within the RPP range of 120 to 80 mmHg was determined by calculating an autoregulatory index (AI) for each parameter using the formula AI = (%delta blood flow)/(%delta RPP). An AI of 0 indicates perfect autoregulation, and an index of 1 indicates a system with a fixed resistance. The AI for RBF averaged 0.33 +/- 0.12 over this pressure range and showed a significantly greater (P < 0.05) autoregulatory ability than did the RMBF (0.82 +/- 0.13). Decreasing perfusion pressure < 80 mmHg produced significant decreases in both RBF and RMBF.(ABSTRACT TRUNCATED AT 250 WORDS)
Reduced febrile responses to pyrogens after lesions of the hypothalamic paraventricular nucleus
Authors: Horn T. , Wilkinson M. F. , Landgraf R. , Pittman Q. J.
Published: December 2017

The hypothalamic paraventricular nucleus (PVN) is recognized as a major site of autonomic control, but the role of this nucleus in thermoregulation is unclear. Therefore the role of the PVN in the febrile response and in the maintenance of normal body temperature was investigated. Conscious, unrestrained rats with chronic lesions of the PVN received intracerebroventricular injections of several doses of prostaglandin (PG) E2 or intraperitoneal applications of Escherichia coli lipopolysaccharide. The body temperatures of both lesioned and sham-operated animals, monitored via radio telemetry, were compared. Intracerebroventricular PGE2 at doses of 10, 25, and 50 ng caused dose-dependent fevers in both PVN-lesioned and sham-operated animals, which at lower doses were smaller in the lesioned animals than in the sham-operated animals. Intraperitoneal lipopolysaccharide application, 50 micrograms/kg body wt, evoked a significantly lower febrile response in PVN-lesioned animals than in controls. The body temperature of PVN-lesioned animals and controls showed no difference during 300 min of exposure to heat (32 degrees C) or cold (7 degrees C). These results suggest that the PVN contributes to the complex regulation of temperature during the febrile response but not during the maintenance of normal body temperature.
Coordination of the cardiac-related discharges of sympathetic nerves with different targets
Authors: Gebber G. L. , Zhong S. , Barman S. M. , Orer H. S.
Published: December 2017

Partial coherence analysis was used to remove the influences of pulse-synchronous baroreceptor nerve activity (as reflected by the arterial pulse) on the coherence of the cardiac-related discharges of sympathetic nerve pairs in unanesthetized decerebrate cats. It can be predicted that the peak at the heart rate frequency in the ordinary coherence function relating the discharges of two nerves will be eliminated by either partialization using the arterial pulse or surgical baroreceptor denervation, if the central circuits controlling the nerves share baroreceptor inputs but are not interconnected. Contrary to this prediction, in many experiments the peak was not eliminated by partialization using the arterial pulse. Moreover, partialization often nonuniformly reduced the peaks at the heart rate frequency in the coherence functions for different nerve pairs. These results are consistent with a model of multiple routes over which baroreceptor influences are distributed to the central circuits controlling different sympathetic nerves. Specifically, we propose that the direct route from the baroreceptors to each of the central circuits is complemented by cross talk among the central circuits.
Temperature regulation in mice during withdrawal from ethanol dependence
Authors: Crawshaw L. I. , O'Connor C. S. , Crabbe J. C. , Hayteas D. L.
Published: December 2017

Temperature regulation during withdrawal from ethanol dependence was studied in mice. Dependence was induced utilizing ethanol vapor inhalation combined with injections of pyrazole, an alcohol dehydrogenase inhibitor. One control group received vehicle (0.9% NaCl); another received pyrazole (68.1 mg/kg) in vehicle. During withdrawal, mice were placed in a thermal gradient, with core temperature (Tc) and preferred temperature (Tpref) continuously recorded for 26 h. During the period of maximal withdrawal severity (4-10 h after removal from ethanol vapor), the withdrawal group was more active than controls. Withdrawal group Tc [36.4 +/- 0.1 (SE) degrees C] was similar to that of NaCl (36.2 +/- 0.1 degrees C) and pyrazole (36.3 +/- 0.2 degrees C) controls. Withdrawal group Tpref (30.5 +/- 0.5 degrees C) was significantly lower than either NaCl (33.5 +/- 0.3 degrees C) or pyrazole (32.9 +/- 0.5 degrees C) controls. Analysis of covariance with activity as covariate indicated that the difference between Tc and Tpref was greater for the withdrawal group and was due to more than increased activity. Mice withdrawing at constant temperature (29.5 degrees C) did not show Tc different from that of controls. These results support the conclusion that regulated body temperature is not altered during withdrawal. We propose that the lower Tpref of withdrawing mice represents a means of dissipating excess heat that is partly generated by the hypermetabolic state accompanying withdrawal from ethanol dependence.
Localization and analysis of natriuretic peptide receptors in the gills of the toadfish, Opsanus beta (teleostei)
Authors: Donald J. A. , Toop T. , Evans D. H.
Published: December 2017

The distribution and nature of natriuretic peptide binding sites was determined in the gills of the toadfish, Opsanus beta. Specific 125I-labeled rat atrial natriuretic peptide (rANP) and 125I-labeled porcine C-type natriuretic peptide (pCNP) binding sites were observed on the afferent and efferent filamental arteries and lamellar arterioles, and on the marginal channels of the secondary lamellae. In both section autoradiography and competition assays, the binding of both ligands was completely displaced by 1 microM rANP and 1 microM pCNP, but residual binding was observed with 1 microM of the type C natriuretic peptide receptor (NPR-C)-specific ligand C-ANF. Electrophoresis of gill membranes cross-linked with 125I-rANP showed a major band at 75 kDa and a fainter band at 140 kDa. Both rANP and pCNP significantly stimulated the production of cGMP above basal levels; C-ANF had no stimulatory effect. These data show that the intrafilamental gill vasculature of toadfish contains a major population of natriuretic peptide receptors very similar to mammalian clearance receptors and a smaller population of receptors that are linked to a membrane-bound guanylate cyclase.
Plasma volume conservation in pigeons: effects of air temperature during dehydration
Authors: Carmi N. , Pinshow B. , Horowitz M.
Published: December 2017

We assessed the effects of the ambient air temperature prevailing during dehydration, which included complete water and food deprivation, on plasma volume (PV) conservation in pigeons (Columba livia) exposed to air temperatures of 25 degrees C (n = 7), 36 degrees C (n = 12), and 40 degrees C (n = 24). The pigeons were dehydrated for 65.4, 32.3, and 27.7 h, on average, at 25, 36, and 40 degrees C, respectively. Dehydration rates averaged 5, 10, and 15.2% of initial total body water (TBW) per day at the three air temperatures, in ascending order. Birds exposed to 25 and 36 degrees C maintained PV despite the fact that they lost, on average, 14 and 17.3% of their TBW, respectively. In contrast, PV in pigeons exposed to 40 degrees C decreased by 8.9%, even though the reduction in TBW (17.7%) was similar to that incurred at 36 degrees C. Mean plasma osmolalities reached 347.7, 345.6, and 374.8 mosmol/kgH2O at 25, 36, and 40 degrees C, respectively. No significant changes occurred in hematocrit (Hct) and hemoglobin concentrations (Hb) during dehydration at 25 and 36 degrees C. However, at 40 degrees C Hb increased by 8.2% with no change in Hct, indicating a decrease in red blood cell volume (RBCV). The results of this study suggest that maintenance of PV and RBCV is affected not only by the dehydration level attained but also by the ambient conditions under which dehydration is induced and the rate at which dehydration takes place.
Chronic and selective vasopressin blockade in spontaneously hypertensive rats
Authors: Okada H. , Suzuki H. , Kanno Y. , Yamamura Y. , Saruta T.
Published: December 2017

Chronic effects of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on conscious spontaneously hypertensive rats (SHR) were investigated. SHR and Wistar rats were divided into four groups, groups S-1 to S-4 and W-1 to W-4, respectively. Groups S-1 and W-1 were untreated as control. Groups S-2 and W-2 were treated with V1 antagonist, groups S-3 and W-3 received V2 antagonist, and groups S-4 and W-4 were treated with both of V1 and V2 antagonists. V1 and/or V2 antagonists did not affect degree of blood pressure of W-2, W-3, and W-4 rats, and V1 antagonist, alone or combined with V2 antagonist, slightly reduced increases in blood pressure of S-2 and S-4 rats without significance. However, V2 antagonist induced significantly massive and hyposmolar urine in W-3 rats compared with that in S-3 rats. In conclusion, in SHR, circulating vasopressin contributes to increases in blood pressure via either V1 or V2 receptors less than expected from previous studies with antibodies or peptide antagonists.
Muscarinic inhibition of cardiac norepinephrine and neuropeptide Y release during ischemia and reperfusion
Authors: Haunstetter A. , Haass M. , Yi X. , Kruger C. , Kubler W.
Published: December 2017

It was the aim of the present study to characterize the modulatory effect of muscarinic agonists on the overflow of norepinephrine and neuropeptide Y (NPY) from the in situ perfused guinea pig heart, induced by electrical stimulation of the left stellate ganglion (6 Hz, 5 V, 1 min). The muscarinic agonists oxotremorine (0.01-1 microM) and carbachol (0.1-10 microM) reduced norepinephrine and NPY overflow in a concentration-dependent manner to approximately 30% of control. The inhibitory effect of carbachol was antagonized by the unspecific muscarinic antagonist atropine (1 microM) but not by the nicotinic antagonist hexamethonium (100 microM). The M2-specific antagonist AF-DX-116BS was 25 times more potent than the M1-specific antagonist pirenzepine in antagonizing the inhibitory effect of carbachol [50% inhibitory concentration (IC50) = 0.2 microM for AF-DX-116BS; IC50 = 5.0 microM for pirenzepine]. These findings indicate that presynaptic muscarinic inhibition of stimulated norepinephrine and NPY release from the guinea pig heart is mediated mainly by activation of M2 receptors. As early as 2 min after stop-flow ischemia, the inhibitory effect of carbachol (10 microM) on the stimulation-evoked overflow of norepinephrine and NPY was lost. On reperfusion with oxygenated buffer after 10 min of stop-flow ischemia the inhibitory effect of carbachol (10 microM) on stimulation-induced norepinephrine and NPY overflow recovered within 3 min.
Expression of the angiotensinogen gene is synergistically stimulated by 8-BrcAMP and Dex in opossum kidney cells
Authors: Ming M. , Wang T. T. , Lachance S. , Delalandre A. , Carriere S. , Chan J. S.
Published: December 2017

We transiently transfected fusion genes with the 5'-flanking region of the angiotensinogen gene linked to a bacterial chloramphenicol acetyltransferase (CAT) coding sequence as a reporter into opossum kidney (OK) cells. The addition of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) (10(-3)-10(-7) M) or forskolin (10(-9)-10(-5) M) stimulated the expression of the plasmid pOCAT [angiotensinogen nucleotide (N) -1498/+18] fusion gene in OK cells in a dose-dependent manner. The addition of dexamethasone (Dex) (10(-6) M) further enhanced the stimulatory effect of 8-BrcAMP or forskolin, whereas the addition of (R)-p-adenosine 3',5'-cyclic monophosphorothioate [(Rp)-cAMP[S], an inhibitor of cAMP-dependent protein kinase A, I and II] blocked the stimulatory effect of 8-BrcAMP. Furthermore, the addition of 8-BrcAMP (10(-3) M) or Dex (10(-6) M) or a combination of both stimulated the expression of pOCAT (angiotensinogen N -1138/+18), pOCAT (angiotensinogen N -960/+18), pOCAT (angiotensinogen N -814/+18), and pOCAT (angiotensinogen N -688/+18), but had no effect on the expression of pOCAT (angiotensinogen N -280/+18), pOCAT (angiotensinogen N -198/+18), pOCAT (angiotensinogen N -110/+18), pOCAT (angiotensinogen N -53/+18), and pOCAT (angiotensinogen N -35/+18). To further localize the putative cAMP-responsive element (CRE) in the angiotensinogen gene, we constructed fusion genes by inserting the DNA fragments angiotensinogen N -814 to N -689, angiotensinogen N -814 to N -761, and angiotensinogen N -760 to N -689 of the 5'-flanking region of the angiotensinogen gene upstream of the thymidine kinase (TK) promoter fused to a CAT gene and introduced them into OK cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Suppression of sucrose intake by continuous near-celiac and intravenous cholecystokinin infusions in rats
Authors: Cox J. E. , Perdue G. S. , Tyler W. J.
Published: December 2017

We compared suppression of intake of 30% sucrose produced by continuous aortal (near celiac) and intravenous infusions of cholecystokinin octapeptide (CCK-8). Adult, male Sprague-Dawley rats received 21-min infusions of saline or 100-1,600 ng CCK-8. Sucrose was available for 20 min, beginning 1 min after onset of infusions. Significant reductions in intake were produced by near-celiac infusions of 400, 800, and 1,600 ng CCK-8, but only the two highest doses affected intake when infused intravenously. In a second experiment, which replicated previous observations, near-celiac bolus infusions of 70 ng CCK-8 significantly reduced sucrose intake but intravenous infusions did not. Behavioral observations indicated that although bolus infusions produced immediate disruption of feeding, suggesting an aversive effect, effects of continuous CCK-8 infusions on temporal intake patterns were consistent with enhancement of satiety. These data provide further evidence that CCK-8 acts on a site within the upper gastrointestinal tract to produce satiety.
Apparent lack of beta 3-adrenoceptors and of insulin regulation of glucose transport in brown adipose tissue of guinea pigs
Authors: Himms-Hagen J. , Triandafillou J. , Begin-Heick N. , Ghorbani M. , Kates A. L.
Published: December 2017

Norepinephrine-induced thermogenesis was substantial in adipocytes from brown adipose tissue (BAT) of cold-acclimated guinea pigs but absent in adipocytes from BAT of warm-acclimated guinea pigs. There was no thermogenic response to any beta 3-adrenergic agonist (CL-316,243, ZD-7114, BRL-28410, CGP-12177). The receptor was characterized as a beta 1-adrenoceptor. Adrenergic agonists stimulated adenylate cyclase in membranes from BAT of both warm- and cold-acclimated guinea pigs also via a beta 1-adrenoceptor; beta 3-adrenergic agonists had no effect. Glucose transport by brown adipocytes from warm-acclimated guinea pigs was not stimulated by either norepinephrine or insulin. Cold acclimation induced the appearance of stimulation of glucose transport by norepinephrine in association with the appearance of a large capacity for thermogenesis, but there was little improvement in response to insulin. GLUT4 was present in membranes from BAT of both warm- and cold-acclimated guinea pigs. Insulin is known to have an antilipolytic effect on both BAT and white adipose tissue of guinea pigs. Thus there is a selective lack of insulin-regulated glucose transport that is not improved by cold acclimation. Guinea pigs may have a mutated component of the translocation mechanism for GLUT4. beta 3-Adrenoceptors appear to be absent in brown adipocytes of adult guinea pigs, as in white adipocytes of guinea pigs, yet are known to be present in the gut. Tissue-specific expression of beta 3-adrenergic receptors in guinea pigs may differ from that in rats, in which receptors are expressed in the adipose tissues and gut.
Adaptive resetting of the volume control of vasopressin secretion during sustained hypovolemia
Authors: Iwasaki Y. , Gaskill M. B. , Robertson G. L.
Published: December 2017

To determine the effect of sustained hypovolemia on vasopressin secretion, we studied rats after 1-32 h of diuretic therapy. We found that an injection of furosemide (10 mg/kg) produced a transient marked increase in urine output, a moderate 7-10% reduction in blood volume, and a three- to fourfold rise in plasma vasopressin from 1.6 +/- 0.2 to 5.6 +/- 1.0 pmol/l. When the hypovolemia was maintained by repeated injections of the diuretic, plasma vasopressin remained elevated for > or = 8 h but returned almost to normal by 32 h, even though plasma electrolytes, blood pressure, hematocrit, and the other measures of hypovolemia were unchanged. At this time, pituitary vasopressin was undiminished, and plasma vasopressin rose normally or even supranormally when an acute hypovolemic or osmotic stimulus (intraperitoneal polyethylene glycol or hypertonic saline) was superimposed. However, the lines describing the relationship of log plasma vasopressin to plasma volume and plasma sodium in the rats treated with furosemide for 32 h lay to the left of the same relationships in the rats treated for 8 h or the sham-treated controls. We conclude that, in rats, the vasopressin response to sustained hypovolemia persists for > or = 8 h but is markedly diminished by 32 h. The decline in plasma vasopressin during this interval appears to be due to adaptive resetting of the volume control mechanism.
Systemic hemodynamics and renal function during long-term pathophysiological increases in circulating endothelin
Authors: Wilkins F. C. , Alberola A. , Mizelle H. L. , Opgenorth T. J. , Granger J. P.
Published: December 2017

Although recent studies have reported endogenous plasma endothelin levels to be elevated two- to fivefold in chronic pathophysiological states, whether such an increase in circulating endothelin levels alone can lead to significant long-term alterations in cardiovascular and renal function is not known. The purpose of this study was to examine the long-term systemic hemodynamic and renal effects of a pathophysiological increase in plasma endothelin concentration in chronically instrumented, conscious dogs (n = 7). Infusion of endothelin-1 (2.5 ng.kg-1.min-1) for 8 days increased plasma concentration of immunoreactive endothelin approximately two- to threefold from 6.7 +/- 0.4 to 16.0 +/- 2.2 pg/ml. Mean arterial pressure increased 21% from a control value of 86.7 +/- 2.1 to 105.0 +/- 2.5 mmHg during the endothelin infusion period. Cardiac output averaged 2,200 +/- 205 ml/min during control and fell by 33% on day 4 of endothelin infusion (1,484 +/- 146 ml/min) and was still 14% below control after day 8 of endothelin infusion (1,885 +/- 154 ml/min). Endothelin increased total peripheral resistance from 42.0 +/- 3.1 to 80.3 +/- 9.1 mmHg.l-1.min. Increasing plasma endothelin two- to threefold was associated with an increase in renal vascular resistance and decreases in glomerular filtration rate and renal plasma flow. Endothelin-1 had no long-term effect on plasma renin activity or aldosterone concentration. These data indicate the importance of pathophysiological levels of endothelin in controlling renal and cardiovascular function in chronic conditions. Furthermore, the results indicate that endothelin may play a role as a mediator of chronic hypertension in pathophysiological states associated with endothelial dysfunction.
Neuropeptide Y fails to increase intraoral intake in rats
Authors: Seeley R. J. , Payne C. J. , Woods S. C.
Published: December 2017

Neuropeptide Y (NPY) has a potent orexigenic effect when administered either into the third ventricle or directly into hypothalamic nuclei, but the mechanism by which NPY increases intakes is poorly understood. The present study tested the ability of NPY to increase intake of the rat in the intraoral intake test, which focuses on the highly stereotyped consummatory phase of ingestion by introducing a 0.1 M sucrose solution directly into the oral cavity of rats via indwelling intraoral cannulas. Doses of 3, 9.5, and 30 micrograms of NPY, when administered into the third ventricle, all failed to change intraoral intake compared with a saline control. Food deprivation (24 h), however, nearly doubled intraoral intake. Additionally, in separate experiments, 9.5 micrograms of NPY significantly increased both 1-h food intake and 1-h bottle intake of 0.1 M sucrose. These results are consistent with two conclusions. 1) NPY does not affect the consummatory phase of ingestion. 2) NPY administration does not completely mimic the stimulus state associated with food deprivation, since food deprivation but not NPY administration increases intake in the intraoral intake test.
Diet-independent suppression of ingestive behavior by cholecystokinin octapeptide and amino acids
Authors: Mamoun A. H. , Anderstam B. , Bergstrom J. , Qureshi G. A. , Sodersten P.
Published: December 2017

Male rats consumed much more of an intraorally administered mixed protein, fat and carbohydrate solution than of a carbohydrate solution. Injection of cholecystokinin octapeptide (CCK-8, 0.6-5.0 microgram) suppressed intake of both solutions, but the CCK-A receptor antagonist L-364, 718 (20-40 micrograms) facilitated only carbohydrate intake. Blood levels of CCK-8 were higher after intake of the carbohydrate than the mixed solution. Blood levels of isoleucine, leucine, lysine, threonine, valine, and tryptophan increased only after intake of the mixed solution. Injection of these amino acids suppressed intake of both solutions. Blood levels of amino acids were also less after the seventh than after the first session ingesting the mixed solution. Treatment with CCK-8 or amino acids inhibits intake of any diet, but when secreted endogenously, these signals may terminate the meal in a diet-dependent manner.