bluuebunny/crossref_metadata_2025 huggingface dataset:
High blood pressure maintenance in transgenic mRen-2 vs. Lyon genetically hypertensive rats
Authors: Lo M. , Medeiros I. A. , Mullins J. J. , Ganten D. , Barres C. , Cerutti C. , Vincent M. , Sassard J.
Published: December 2017

The present work was aimed to assess the factors involved in the maintenance of hypertension in adult transgenic mRen-2 (TG) rats. Special attention was paid to the renal handling of sodium, the sympathetic, and the renin-angiotensin system (RAS) activity. TG rats were compared with age-matched Lyon genetically hypertensive rats (LH), as both are of Sprague-Dawley origin. Blood pressure (BP), heart rate, and renal sympathetic nerve activity (RSNA) were recorded in conscious freely moving animals. Kidneys were isolated and single-pass perfused at different pressure levels. It was observed that the peripheral sympathetic drive was identical in TG and LH rats as indicated by their similar 24-h urinary excretion of catecholamines and methoxylated metabolites, baseline RSNA and its control by the baroreflex, and hypotensive response to ganglion-blockade. On the contrary, TG rats differed from LH rats by a more rapid excretion of an oral isotonic sodium load, a greater hypotensive and natriuretic response to furosemide, and a more marked BP response to acute RAS blockade. The TG kidney responses to stepwise changes in renal perfusion pressure (RPP) differed from those of LH rats by significantly higher perfusate flow and glomerular filtration rate. However, the pressure natriuresis curve of TG kidneys did not differ from that of LH rats because of an elevated tubular sodium reabsorption rate. These results suggest that adult TG rats, compared with LH rats, exhibit a tendency toward sodium and water retention, which may explain that despite low renal and circulating renin levels, the RAS remains involved in the maintenance of high BP in that model.
Hormonal, fluid, and electrolyte responses of sheep during chronic intravenous infusion of epidermal growth factor
Authors: Gow C. B. , Phillips P. A. , Chandler K. D. , Moore G. P.
Published: December 2017

Epidermal growth factor (EGF) has been shown to increase water intake and urine volume. To further characterize these responses the effects of EGF on fluid balance, electrolyte, and hormone profiles were examined. After an 8-day control period, ewes received intravenous EGF at doses of 0 (n = 6), 2 (low dose, n = 6), 10 (medium dose, n = 6), or 20 micrograms/h (high dose, n = 5) for 4 days. During EGF treatment, water intake and urine volume increased (both P < 0.001) in a dose-related fashion, although fluid balance was unaffected. Feed intake and fecal dry matter output were reduced (both P < 0.001) by the two higher doses of EGF. EGF had no effect on plasma potassium, sodium, or osmolality, but there was a dose-related natriuresis (P < 0.001). Treatment with EGF increased plasma renin activity and aldosterone in the medium and high dose groups (both P < 0.001). Thus chronic intravenous infusion of 10-20 micrograms EGF/h into sheep caused polydipsia, polyuria, and natriuresis with neutral fluid balance. Whether the resultant polydipsia or polyuria was the primary response to EGF remains unclear.
Adrenalectomy of the obese Zucker rat: effects on the feeding response to enterostatin and specific mRNA levels
Authors: Okada S. , Onai T. , Kilroy G. , York D. A. , Bray G. A.
Published: December 2017

The effects of adrenalectomy on the feeding response to enterostatin and the mRNA levels of its parent protein, pancreatic colipase, have been investigated in lean (fa/?) and genetically obese (fa/fa) rats. Adrenalectomy reduced body weight gain and food intake of obese rats. Enterostatin inhibited the intake of high-fat diet in obese rats but not in lean rats. Adrenalectomy reduced food intake of all rats and abolished the response to enterostatin in the obese group. Obese rats had low levels of colipase mRNA, but these were normalized after adrenalectomy. The ability to respond to exogenous enterostatin is possibly linked to low levels of production of the peptide. The effects of adrenalectomy on brown adipose tissue uncoupling protein (UCP) mRNA and beta 3-adrenergic receptor (beta 3-AR) mRNA were also investigated. Northern blot analysis showed low levels of both UCP mRNA and beta 3-AR mRNA in obese rats that were restored to or toward the normal levels of lean rats by adrenalectomy. Adrenalectomy had no significant effects on mRNA levels in lean rats.
Chronic alcohol consumption increases sensitivity to the anorexic effect of cholecystokinin
Authors: Weatherford S. C. , Figlewicz D. P. , Park C. R. , Woods S. C.
Published: December 2017

In this study we examined the ability of intraperitoneal cholecystokinin COOH-terminal octapeptide (CCK-8; 0.2, 0.6, and 2.0 micrograms/kg) to suppress food intake in rats that had consumed a control diet, 6-8 g.kg-1.day-1 of ethanol (EtOH) in sucrose, or sucrose alone for 6 mo. Both the EtOH- and sucrose-fed rats developed significant dietary obesity. After 3 mo, the EtOH group was significantly more sensitive to CCK-8 than the sucrose and control groups, while the responses of the sucrose and control groups were comparable. In contrast, after 6 mo the EtOH and sucrose groups' response to CCK-8 was no longer significantly different. After 6 mo there were no significant differences in basal or postprandial plasma CCK-8 levels. The sucrose group had significantly higher basal insulin levels than the control and EtOH groups, and postprandial insulin levels, relative to basal, were significantly elevated in the EtOH group. Basal glucose levels did not differ among groups. Postprandial glucose levels (relative to baseline) were significantly lower in the EtOH group compared with the other groups and in fact never rose above baseline levels. These results are consistent with the hypothesis that EtOH, when taken on a chronic basis, increases the sensitivity to CCK-8.
Integration of oral habituation and gastric signals in decerebrate rat pups
Authors: Swithers-Mulvey S. E. , Hall W. G.
Published: December 2017

During a series of oral infusions of a sweet solution, the ingestive responses of young rat pups habituate; pups stop responding to the infusions even when their stomachs are empty and the infused diet is nonnutritive. The rate of this oral habituation is enhanced by the addition of gastric fill signals, even in decerebrate pups. In intact but not in decerebrate pups, prior deprivation gates out the influence of gastric fill on habituation. This oral habituation system, responsive to multiple ingestion-related signals, may serve as the elemental process that integrates physiological state with ongoing behavior to control ingestion.
Effects of centrally and systemically administered indomethacin on body temperature in exercising rats
Authors: Tanaka H. , Yanase-Fujiwara M. , Kanosue K.
Published: December 2017

Subcutaneous and intracerebroventricular (icv) injections of indomethacin were used to test whether prostaglandin synthesis is essential for the exercise-induced increase in a rat's body temperature. At an air temperature of 24 degrees C, male Wistar rats ran on a treadmill at 10-15 m/min 20 min after 300-micrograms icv injection or 60 min after 15-mg/kg sc injection of indomethacin or of control vehicle. The rectal temperature (Tre) of control rats in 17 control experiments increased by 1.0 degree C during exercise, whereas the Tre of the rats pretreated with intracerebroventricular indomethacin increased by only 0.4 degrees C. Threshold Tre for tail vasodilation was significantly lower in rats pretreated with indomethacin than the control rats (38.4 +/- 0.1 vs. 38.9 +/- 0.1 degrees C), but O2 uptake did not differ between indomethacin-pretreated and control rats. Subcutaneous injection of indomethacin did not affect the body temperature, tail vasomotor activity, or O2 uptake of exercising rats. Intracerebroventricular indomethacin did not affect Tre or tail vasomotor activity of rats resting at ambient temperatures of 24 and 28 degrees C. Present results suggest that prostaglandin synthesis is required for the vasoconstrictive effect of exercise on skin blood vessels and thus for the exercise-induced elevation of body temperature.
Effects of renal receptor stimulation on neurons within the ventrolateral medulla of the cat
Authors: Vizzard M. A. , Standish A. , Ammons W. S.
Published: December 2017

Experiments were performed to determine if activation of renal receptors by occlusion of the renal artery, renal vein, or ureter would alter activity of cells within the ventrolateral medulla of the cat. Extracellular unit recordings were obtained from 195 cells located within the rostral ventrolateral medulla of 90 alpha-chloralose-anesthetized cats. Fifty-five of 195 cells (28.2%) tested for responses to renal receptor activation responded to at least one of the occlusions. Occlusion of the ureter increased the activity of 25 cells from 9.7 +/- 3.7 to 23.0 +/- 6.5 impulses/s and decreased the activity of 5 cells from 11.9 +/- 3.6 to 3.5 +/- 1.2 impulses/s. Occlusion of the renal vein increased the activity of seven cells from 7.5 +/- 3.3 to 22.3 +/- 7.3 impulses/s and decreased the activity of six cells from 13.8 +/- 3.8 to 4.1 +/- 2.0 impulses/s. Renal artery occlusion elicited solely excitatory responses from 43 cells. Thirty-one of the 43 cells increased their activity within 0-3 s of the onset of renal artery occlusion from 4.1 +/- 0.8 to 12.6 +/- 1.2 impulses/s. Renal artery occlusion increased the activity of 10 out of 43 cells with a mean latency of 26.1 +/- 6.5 s from 8.3 +/- 2.5 to 29.6 +/- 9.3 impulses/s. Twenty-four of the 55 (43.6%) responders were responsive to two or more forms of renal receptor activation. These results demonstrate that activation of renal mechanoreceptors and chemoreceptors affects cells within the ventrolateral medulla of the cat.(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular effects of arginine vasotocin in toad skin
Authors: Malvin G. M.
Published: December 2017

Fluid balance in amphibians is regulated, in large part, by arginine vasotocin (AVT). One important action of this hormone is to facilitate water uptake by increasing the water permeability of the skin. Cutaneous blood flow also affects water uptake, but the effects of AVT on skin perfusion are unknown. This study tested the hypothesis that AVT facilitates water uptake, not only by increasing cutaneous water permeability, but also by promoting cutaneous blood flow. The effects of AVT on blood flow through the ventral pelvic skin, a region specialized for water uptake, were assessed in Bufo marinus by determining the conductance of the skin to acetylene (GsAc), an index of cutaneous blood flow. A pump-perfused skin preparation was used to study the effects of AVT on the cutaneous vascular resistance (CVR) of the ventral pelvic skin and the dorsal skin (a region not normally involved in water uptake). Bolus AVT injections (iv) of 10 pmol/kg and below had no significant effect on GsAc (P > 0.45). However, 100 and 300 pmol/kg of AVT decreased GsAc by 39 +/- 7 (P < 0.001) and 63 +/- 6% (P < 0.001), respectively. The higher AVT doses increased mean arterial pressure. AVT increased CVR in both pump-perfused preparations. The lowest concentration of AVT tested that significantly raised CVR was 1 x 10(-10) M for the dorsal skin (P = 0.006) and 3 x 10(-10) M for the ventral pelvic skin (P = 0.038).(ABSTRACT TRUNCATED AT 250 WORDS)
Role of mu 1- and delta-opioid receptors in modulation of fetal EEG and respiratory activity
Authors: Cheng P. Y. , Wu D. , Soong Y. , McCabe S. , Decena J. A. , Szeto H. H.
Published: December 2017

Recent evidence suggests that administration of low doses of morphine causes respiratory stimulation, along with a more active electroencephalogram (EEG) in the fetal lamb. The present study used selective opioid agonists and antagonists to determine the role mu 1- and delta-opioid receptor subtypes play in the response as well as determine if endogenous opioid peptides exert a tonic influence at the mu 1- and delta-opioid receptors to maintain normal EEG and respiratory activity under control, physiological conditions. Both morphine (2.5 mg/h iv) and [D-Pen2,D-Pen5]enkephalin (DPDPE) (46 nmol/h icv) resulted in a significant activation of fetal EEG, which was blocked by naloxonazine (NALZ, mu 1-opioid antagonist) and naltrindole (NTI, delta-opioid antagonist), respectively. Administration of NALZ alone, but not NTI, resulted in a slowing of the EEG. Morphine and [D-Ala2]deltorphin I (0.36 nmol/h icv) significantly increased breath number and were blocked by NALZ and NTI respectively. Both NALZ and NTI alone resulted in a reduction in breath number. These results suggest that the activation of the delta- or mu 1-opioid receptors will stimulate fetal respiratory and EEG activity. Furthermore, the endogenous opioids play a tonic role at both the delta- and mu 1-opioid receptors in the regulation of respiratory timing and EEG activity.
Exercise, unlike insulin, promotes glucose transporter translocation in obese Zucker rat muscle
Authors: King P. A. , Betts J. J. , Horton E. D. , Horton E. S.
Published: December 2017

Insulin or exercise stimulates skeletal muscle glucose transport, most likely by increasing both the number and activity of glucose transporters in the plasma membrane. Skeletal muscle glucose transport of genetically obese Zucker rats (fa/fa) displays a severe insulin resistance that results, at least in part, from a failure of net transporter translocation to the cell membrane (King, P., E. D. Horton, M. Hirshman, and E. S. Horton. J. Clin, Invest. 90: 1568-1575, 1992). The purpose of the present study was to determine if the obese rat muscle was also resistant to the action of acute exercise to increase glucose transport and, if so, to determine if the defect involved transporter translocation as seen in the resistance to insulin. The muscle glucose transport system was investigated in plasma membranes isolated from postprandial, sedentary or acutely exercised, lean and obese Zucker rats. Measurements of D- and L-glucose uptake by membrane vesicles under equilibrium exchange conditions indicated that an acute bout of exercise resulted in a threefold increase in the maximum velocity (Vmax) for lean animals (5.7 vs. 17.6 nmol.mg protein-1.min-1) and a 4.5-fold increase in the Vmax for obese rats (4.1 vs. 18.6 nmol.mg protein-1.min-1). For both lean and obese animals, this increase in transport was associated with an increase in transporter number measured by cytochalasin B binding (1.6- and 2.2-fold, respectively) and with an increase in the average carrier turnover number (1.9- and 2.0-fold, respectively). The results indicate that, unlike a maximal insulin stimulus, acute exercise of the obese Zucker rat promotes both transporter translocation and transporter activation in skeletal muscle.
Nonadrenergic noncholinergic autonomic mediation of pressor response to feeding in lambs
Authors: Jones S. A. , Langille B. L. , Frise S. , Adamson S. L.
Published: December 2017

We examined factors mediating a 70% increase in arterial blood pressure that occurs during feeding in newborn lambs. We report that the increase in blood pressure during feeding was significantly reduced (to approximately 50%) and delayed in onset by combined alpha- and beta-adrenergic blockade. Plasma angiotensin and vasopressin levels did not increase significantly during feeding, nor was the pressor response to feeding attenuated while using captopril to block the production of angiotensin II. Adrenalectomy or muscarinic cholinergic blockade with atropine was also unsuccessful in attenuating the pressor response to feeding. We demonstrated that the component of the pressor response to feeding that was insensitive to alpha, beta, and muscarinic blockade was mediated by the autonomic nervous system because it was completely eliminated by ganglionic blockade with hexamethonium. Thus nonadrenergic noncholinergic autonomic mechanisms mediate approximately half the pressor response to feeding in lambs.
Autonomic modulation of ovine fetal responses to atrial natriuretic factor infusion
Authors: Bayer L. A. , Cheung C. Y. , Brace R. A.
Published: December 2017

The aim of this study was to determine whether the autonomic nervous system modulates the cardiovascular, endocrine, and/or urinary responses to atrial natriuretic factor (ANF) infusion in the fetus. We infused ANF intravenously for 30 min into chronically catheterized, late-gestation sheep fetuses with autonomic blockade and compared the responses to those in autonomically intact fetuses. During the infusions, plasma ANF concentration increased similarly in the blocked and intact fetuses. Arterial pressure decreased by 2 mmHg in both groups, but the decrease occurred earlier in the blocked fetuses. Heart rate was significantly decreased by an average of 15 beats/min in the blocked compared with the intact fetuses. Plasma protein concentration decreased in the blocked fetuses compared with a rise in the intact fetuses. In the blocked fetuses, the restoration of blood volume to normal during the postinfusion period occurred earlier. In the blocked animals, low doses of ANF produced a diuresis, whereas high doses did not increase urine flow; the opposite responses occurred in the intact group. Plasma arginine vasopressin (AVP) concentration increased during the infusion only in the blocked animals. The fetal venous pressure, plasma renin activity, and norepinephrine responses were similar in both groups. These data suggest that the autonomic nervous system may play a role in modulating the fetal arterial pressure, heart rate, blood volume, plasma protein concentration, AVP, and urine flow responses to ANF. Thus the autonomic nervous system appears to significantly modulate multiple responses to ANF in the late-gestation ovine fetus.
Increased uteroplacental production of prostaglandin E2 during ethanol infusion
Authors: Bocking A. D. , Sinervo K. R. , Smith G. N. , Carmichael L. , Challis J. R. , Olson D. M. , Brien J. F.
Published: December 2017

Experiments were conducted in 14 pregnant sheep to determine the effect of a 1-h maternal infusion of ethanol (1 g/kg maternal body wt) on placental efflux of prostaglandin E2 (PGE2), umbilical blood flow (Qum), and carbohydrate metabolism at 123-130 days gestation. This ethanol dosage regimen produced peak ethanol concentrations in fetal and maternal blood in the range of 1.48-1.64 mg/ml at the end of the infusion. Umbilical venous and fetal arterial PGE2 concentrations increased (P < 0.05) from 315 +/- 47 and 202 +/- 25 pg/ml to 740 +/- 172 and 489 +/- 67 pg/ml, respectively, at the end of the infusion. Placental secretion of PGE2 into the fetal circulation increased by 45% (P < 0.05). Uterine venous and maternal arterial PGE2 concentration increased (P < 0.05) from 370 +/- 27 and 262 +/- 28 pg/ml to 705 +/- 51 and 487 +/- 69 pg/ml, respectively. Fetal and maternal blood glucose concentration decreased (P < 0.05) from 0.98 +/- 0.11 and 2.88 +/- 0.25 mmol/l to 0.81 +/- 0.21 and 2.44 +/- 0.16 mmol/l, respectively. Fetal and maternal blood lactate concentration increased (P < 0.05) from 1.40 +/- 0.11 and 0.68 +/- 0.07 mmol/l to 1.67 +/- 0.14 and 1.82 +/- 0.16 mmol/l, respectively. Qum, fetal heart rate, fetal blood pressure, and fetal and maternal blood gases were unchanged by the ethanol infusion. These results support the hypothesis that the placenta is the major source of the elevated fetal and maternal plasma PGE2 concentrations produced in pregnant sheep by maternal ethanol administration.
Physiological responses of freeze-tolerant and -intolerant frogs: clues to evolution of anuran freeze tolerance
Authors: Costanzo J. P. , Lee R. E. , Lortz P. H.
Published: December 2017

Freeze tolerance in the wood frog, Rana sylvatica, is promoted by multiple, integrated physiological responses to ice forming within body tissues. By analyzing the freezing responses of the sympatric, but freeze intolerant, leopard frog (R. pipiens), we sought clues to the evolution of anuran freeze tolerance. Physiological responses critical to R. sylvatica's freeze tolerance, such as the synthesis and distribution of the cryoprotectant glucose, protective dehydration of organs, and deferred cardiac failure, were present, but comparatively less pronounced, in R. pipiens. Both species were innately tolerant of hyperglycemia. Glucose supplements did not enhance the freezing viability of R. pipiens, although in vitro tests of cryoprotectant efficacy revealed that glucose and glycerol provided comparable protection to erythrocytes of both species. We conclude that the evolution of freeze tolerance in R. sylvatica is not only promoted by its desiccation tolerance and the fortuitous biophysical consequences of freezing (e.g., exothermic induction of cardioacceleration and moderation of cooling rate) but also involves a progressive enhancement of fundamental physiological stress responses.
Differential effects of proteinase inhibitor camostat on exocrine pancreas in fed and fasted rats
Authors: Otsuki M. , Tani S. , Fujii M. , Nakamura T. , Okabayashi Y. , Koide M.
Published: December 2017

Effects of an oral dose of the synthetic trypsin inhibitor camostat on pancreatic exocrine function were examined in rats that were either fasted from 12 h before feeding camostat to the end of experiments or fed ad libitum. Camostat (100 mg/kg body wt) caused significant increases in plasma cholecystokinin bioactivity (peak 13.4 +/- 2.0 pM at 30 min for fasted rats vs. 16.6 +/- 1.7 pM at 2 h for fed rats; not significant) and pancreatic exocrine secretion. In fed rats, but not in fasted rats, significant increases in pancreatic exocrine secretion were observed again at 12 h after a single oral dose of camostat (juice flow 10.3 +/- 0.4 microliters/20 min in fasted rats vs. 175.5 +/- 17.8 microliters/20 min in fed rats; P < 0.001), although pancreatic juice flow in fed and fasted control rats was nearly the same. When the pancreata from camostat-pretreated rats were isolated and perfused, the early effects of camostat on pancreatic exocrine secretion were abolished, whereas the late effects (12 h postfeeding) in fed rats were still observed (juice flow 33.7 +/- 3.4 microliters/20 min vs. control 2.8 +/- 0.4 microliters/20 min; P < 0.001). Thus, in addition to humoral and neural factors, persistent functional changes might have occurred in the pancreas of the fed camostat-pretreated rats. These present results indicate that oral camostat induces two different effects, immediate and delayed, on pancreatic exocrine secretory function. Camostat exerts its immediate effects in both fed and fasted rats, whereas delayed effects were induced only in fed rats.
Role of periaqueductal gray in the pressor response produced by central injections of angiotensin II
Authors: Portis L. R. , Lewis S. J. , Brody M. J.
Published: December 2017

The present studies were undertaken to determine the role of rostral periaqueductal gray (PAG) in mediating the pressor effect produced by intracerebroventricular (icv) injection of angiotensin II (ANG II, 200 ng). Two functionally and anatomically distinct sites were identified in rostral PAG: a dorsomedial site involved in the hemodynamic responses produced by electrical stimulation of the anteroventral third ventricle (AV3V) region and a ventromedial site required for the pressor response elicited by icv administration of ANG II. In Saffan-anesthetized rats, injection of lidocaine (LIDO, 4%) in dorsomedial PAG, but not in ventromedial PAG, significantly attenuated the decrease in hindquarter resistance (HQR) produced by electrical stimulation of the AV3V region, and the poststimulatory increase in mean arterial pressure (MAP) and HQR. The injection of LIDO in ventromedial PAG had no effect on the hemodynamic responses produced by electrical stimulation of the AV3V region in anesthetized rats but significantly attenuated the pressor response produced by icv administration of ANG II in conscious rats. The hypothesis that these two sites receive separate projections was addressed by microinjecting two retrogradely transported fluorescent dyes, Fluoro-Gold and Fast Blue. The anatomic findings suggest that separation of the pathways activated by electrical and chemical stimulation of the AV3V region occurs at the level of rostral PAG.
Cold-defense function of brown adipose tissue during sleep
Authors: Calasso M. , Zantedeschi E. , Parmeggiani P. L.
Published: December 2017

Rats with chronically implanted electroencephalograph scalp electrodes and thermistors were exposed to 24 and 4 degrees C ambient temperatures during the light hours before and after acclimation to 4 degrees C ambient temperature for 9 days. During synchronized sleep, deep interscapular temperature was higher at 4 degrees C than at 24 degrees C both before and after acclimation to cold. After ablation of brown adipose tissue, deep interscapular temperature was lower at 4 degrees C than at 24 degrees C during synchronized sleep. In the presence of brown adipose tissue, deep interscapular temperature decreased sharply during desynchronized sleep at 4 degrees C both before and after acclimation to cold. This decrease was subsequent to and correlated with an increase in the temperature of the nasal mucosa. The decrease in deep interscapular temperature during desynchronized sleep at 4 degrees C ambient temperature was markedly reduced by ablation of the interscapular brown adipose tissue.
Sustained sleep deprivation impairs host defense
Authors: Everson C. A.
Published: December 2017

Prolonged sleep deprivation in rats causes an unexplained hypercatabolic state, secondary malnutrition symptoms, and mortality. The nature of the vital impairment has long been a mystery. Its determination would help to elucidate the type of organic dysfunction that sleep prevents. There are no gross detectable disturbances in intermediary metabolism, clinical chemistry, or hematological indexes that provide substantial clues to the mediation of sleep-deprivation effects. Furthermore, postmortem examinations reveal no systematic morphological or histopathological findings. Taken together, the cachexia and the absence of evidence of structural damage or organ dysfunction pointed to involvement of a regulatory system that was diffuse, possibly the immune system. Blood cultures revealed invasion by opportunistic microbes to which there was no febrile response. These results suggest that the life-threatening condition of prolonged sleep deprivation is a breakdown of host defense against indigenous and pathogenic microorganisms.
Metabolic and neurochemical profiles in insulin-treated diabetic rats
Authors: Bellush L. L. , Reid S. G.
Published: December 2017

Plasma glucose concentration was measured at 3-h intervals in streptozotocin-induced diabetic rats placed on various insulin replacement regimens using three different kinds of insulin. High insulin dosages produced at least periodic hypoglycemia, even though there were no overt signs of insulin overdose. Low- and single-dose regimens produced periods of hyperglycemia. Both high and low doses of protamine zinc insulin normalized diabetes-induced reductions in 5-hydroxyindole-3-acetic acid [5-HIAA; the principal metabolite of 5-hydroxytryptamine (5-HT)] and 5-HT turnover (5-HIAA/5-HT), despite the failure of the low-dose regimen to normalize plasma glucose. Diabetic rats evidenced continued hyperphagia and hyperdipsia during insulin treatment, and insulin treatment also induced hyperphagia and excessive weight gain in nondiabetic rats. Insulin treatment only partially normalized diabetes-induced adrenal hypertrophy. Adrenal hypertrophy is an indication of a continued stresslike physiological state in diabetes even during insulin therapy. This state may be involved in the enhanced risk in diabetic humans for development of anxiety disorders and clinical depression.
Mechanisms of pressor and bradycardic responses to L-glutamate microinjected into the NTS of conscious rats
Authors: Colombari E. , Bonagamba L. G. , Machado B. H.
Published: December 2017

Microinjection of increasing doses of L-glutamate (L-Glu, 0.03-5.0 nmol/100 nl) into the nucleus tractus solitarii (NTS) produced a dose-related pressor and bradycardic response. Prazosin virtually abolished the pressor response but produced no changes in the bradycardic response to L-Glu, indicating that bradycardia is not reflex in origin. The bradycardic response was blocked by atropine. In three different groups of rats, excitatory amino acid receptors in the NTS were blocked by increasing doses of kynurenic acid (0.5, 2.0, and 10.0 nmol/100 nl) and the pressor and bradycardic responses to L-Glu (1 nmol/100 nl) were reduced in a dose-related pattern. Reflex bradycardia induced by an increase in pressure caused by phenylephrine (iv) was also blocked by kynurenic acid. These data show that microinjection of L-Glu into the NTS of conscious rats produced pressor and bradycardic responses, which are due to the activation of two independent autonomic pathways. The data also indicate that the activation of both pathways is mediated by excitatory amino acid receptors. Considering that reflex bradycardia was also blocked by kynurenic acid, we suggest that L-Glu and excitatory amino acid receptors are part of the parasympathetic limb of the baroreceptor reflex. The pressor response to L-Glu is also mediated by excitatory amino acid receptors, but its physiological meaning is still unclear.
Role of vagal afferents in hypotension induced by venous air embolism
Authors: Aibiki M. , Ogura S. , Seki K. , Honda K. , Umegaki O. , Shirakawa Y. , Ogli K.
Published: December 2017

To evaluate the role of the autonomic nervous system in the development of hypotension during air embolism, we studied the effects of an intravenous bolus injection of air (0.5 ml/kg) on mean blood pressure (MBP), central venous pressure (CVP), and renal nerve activity (RNA) in urethan-anesthetized rabbits of three groups: animals with an intact neuraxis (intact group; n = 5), cervical-vagotomized animals (vagotomy group; n = 5), and sinoaortic-denervated animals (SAD group; n = 5). In the intact group, despite a significant decrease in MBP at 10 s after air injection, RNA did not increase from the preinjection level. This response of RNA was associated with a significant increase in CVP and lasted for 20 s after the injection. Vagotomized animals, however, exhibited a significant augmentation in RNA in response to a drop in MBP at 10 s after the injection. In the SAD group, profound declines in both MBP and RNA were observed at 10 s after the injection of air. Animals in these two groups showed remarkable increases in CVP. At 5 min after the air administration, MBP in the vagotomy group was significantly higher than that in the intact group. All animals in the SAD group died within 5 min of the injection. These results indicate that during hypotension induced by air injection, sympathetic activation through arterial baroreceptors may be depressed by vagal afferents emanating from cardiopulmonary receptors; the results also suggest that the arterial baroreceptor nerves may be required to overcome the lethal events that should occur during venous air embolism.
Vasopressin-induced changes in cardiac vagal tone and oxygen consumption in dogs
Authors: Liard J. F.
Published: December 2017

Experiments were conducted in 63 dogs to determine whether stimulation of vagal tone contributes to the decrease in O2 consumption (VO2) that results from arginine vasopressin (AVP) administration. Vagal stimulation with pilocarpine did not reduce VO2 in conscious dogs. In anesthetized dogs, bilateral electrical cervical efferent vagal stimulation lowered both cardiac output (CO; by 46%) and VO2 (by 22%) over the first 5 min. Between 7 and 11 min of stimulation, CO remained decreased, but VO2 returned to control. Significant increases in left atrial pressure, bradycardia, and a fall in mean arterial pressure accompanied vagal stimulation. All these effects of cervical vagal stimulation were abolished by cardiac denervation and also by pacing. Administration of a selective AVP V1 agonist led to significant reductions of CO and VO2. Cardiac denervation prevented the decrease in VO2 induced by AVP infusion, but not the decrease in CO. During AVP infusions, pacing at a rate slightly higher than control heart rate did not prevent the fall in CO or in VO2, whereas pacing at 150 beats/min prevented part of the fall in VO2. Sinoaortic denervation or atropine treatment prevented the decrease in VO2 resulting from AVP infusion. The combination of alpha- and beta-blockade did not affect the CO or the VO2 response to AVP infusion, nor did naloxone treatment. The administration of atrial or ventricular extracts, but not that of alpha-human atrial natriuretic peptide, led to a significant reduction in VO2. These results are compatible with the hypothesis that AVP infusion increases vagal tone to the heart, which, possibly as a result of increased left atrial pressure and reduced heart rate, may release a factor reducing VO2.
Patterns of respiration and heart rate during wakefulness and sleep in elephant seal pups
Authors: Castellini M. A. , Milsom W. K. , Berger R. J. , Costa D. P. , Jones D. R. , Castellini J. M. , Rea L. D. , Bharma S. , Harris M.
Published: December 2017

Although breath holding during diving has been studied extensively in seals, the recent observation that these mammals also exhibit long-duration apnea while apparently sleeping has not been systematically examined. This project examined sleep apnea in northern elephant seal pups (Mirounga angustirostris). The animals exhibited a sequential sleep pattern of wakefulness-slow-wave sleep (SWS)-rapid eye movement (REM) sleep that resembled the normal pattern of mammalian sleep. The typical respiratory pattern during sleep in 4-mo-old pups consisted of short periods of continuous breathing separated by periods of apnea of up to 12 min. Several cycles of apnea and eupnea could occur during a single sleep episode. Breathing during a sleep cycle occurred only in SWS, never during REM sleep. The eupneic heart rate was characterized by significant sinus arrhythmia, and the apneic heart rate was similar to the minimum value during normal sinus arrhythmia. Patterns of change in breathing and heart rate associated with wakefulness and sleep were similar in seals sleeping underwater and on land. When sleeping underwater, the seals raised their heads to the surface to breathe without awakening. The changes in heart rate associated with normal sinus arrhythmia, sleep apnea, and diving apnea appear to be similar, suggesting regulation by a common homeostatic control mechanism.
Calcitropic effects of recombinant prolactins in Oreochromis mossambicus
Authors: Flik G. , Rentier-Delrue F. , Wendelaar Bonga S. E.
Published: December 2017

Homologous recombinant tilapia prolactin-188 (PRL-I) and tilapia prolactin-177 (PRL-II) were tested for calcitropic activity in tilapia, Oreochromis mossambicus. Injection of PRL-I and PRL-II (4 injections, 12.5 pmol/g, over an 8-day period) induced hypercalcemia that resulted from an enhanced calcium influx via the gills and a decreased calcium efflux. Both PRLs increased the density of the Ca(2+)-transporting Ca(2+)-adenosinetriphosphatase in a plasma membrane preparation of the branchial epithelium. Dose-response studies (doses tested: 0.75-12.5 pmol/g) demonstrated that PRL-I was roughly twofold more potent than PRL-II in inducing hypercalcemia, in enhancing basal levels of cortisol, and in stimulating opercular ionocyte density. PRL-I and PRL-II were equipotent in stimulating the dermal mucocyte frequency. We conclude that in this species PRL-I and PRL-II have calcitropic effects, and that PRL-I is more potent than PRL-II in this respect. We postulate that PRL has corticotrophic activity in this fish.
Levels of active and inactive reninlike enzymes in plasma and reproductive tract of the pregnant wallaby
Authors: Lumbers E. R. , Menzies R. I. , Gibson K. J. , Tyndale-Biscoe C. H.
Published: December 2017

Active and total (acid-activated) levels of a reninlike enzyme (hereafter called renin) were measured in plasma, tissues, and yolk sac fluid of pregnant and postpartum wallabies. Plasma active renin generated angiotensin I (ANG I) from sheep angiotensinogen at 14 +/- 1.3 (SE) ng.ml-1.h-1, whereas acid-activated renin generated ANG I at 33.3 +/- 2.5 ng.ml-1.h-1, i.e., 44.2 +/- 3.7% of renin in plasma was active, and 58 +/- 3.7% was inactive. Inactive renin levels were highest in pregnant animals (P = 0.05). Uterine renin was mainly inactive (95%); levels were 5.1 +/- 1.1 times plasma levels. The levels of renin in nonpregnant uteri were the same as those in pregnant uteri from the same animals. Uterine renin levels did not change with gestation. Pooled acid-activated yolk sac fluid generated ANG I at low rates (0.7 and 1.6 ng.ml-1.h-1); the acid-activated supernatant of a homogenate of pooled fetal membranes generated ANG I at 15 ng.g wet wt-1.h-1. Yolk sac fluid was strikingly different in electrolyte composition from maternal plasma. Its lower osmolality suggests that the membranes separating it from maternal plasma have a low permeability to water. Thus, although eutherian and marsupial mammals diverged 136-164 million years ago, the wallaby, like many eutherian mammals, has inactive renin in blood, in the female reproductive tract, and in fetal membranes.
Intraventricular but not intraparaventricular nucleus metergoline elicits feeding in satiated rats
Authors: Coscina D. V. , Feifel D. , Nobrega J. N. , Currie P. J.
Published: December 2017

Previous research has shown that systemic injections of the nonselective serotonin (5-HT) antagonist metergoline (MET) can stimulate feeding in both rats and humans. Five experiments were conducted to determine if this drug would elicit feeding in otherwise satiated rats after direct injections into the brain. In experiment 1, intraventricular infusions of 100 nmol MET produced reliable enhancements of feeding for 1 h compared with control infusions of a 5% tartaric acid (vehicle) solution. In experiment 2, a dose-response study of 0, 50, 100, and 150 nmol MET intraventricularly revealed that both 100 and 150 nmol doses reliably enhanced 1-h feeding, whereas 50 nmol did not. In experiment 3, tests of 90-min locomotor activity and water intake in the absence of food revealed that 100 nmol MET intraventricularly did not modify either behavior compared with vehicle infusions, suggesting a degree of feeding specificity to this effect. In an attempt to determine the site of intraventricular MET effects on feeding, experiment 4 tested 1-h feeding responses after 0, 5, 10, 20, 40, or 60 nmol MET were infused unilaterally into the paraventricular nucleus (PVN) of the hypothalamus. No reliable feeding was induced at any of these drug doses, although injections of 30 nmol norepinephrine (NE) were effective in doubling food intake. Experiment 5 further showed that bilateral infusions of 50 nmol MET in each PVN (total dose, 100 nmol) were ineffective in altering 1-h feeding. This contrasted markedly to the high potency of 15 nmol NE per site (total dose, 30 nmol), which elicited fivefold greater feeding than control infusions.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased lymphatic pressure without increased neck vein pressure during intravenous infusions
Authors: Gabel J. C. , Dhother S. , Drake R. E.
Published: December 2017

Postnodal intestinal lymphatic pressure increases during rapid intravenous infusions with Ringer solution in sheep. Part of the lymphatic pressure increase is due to increased venous pressure at the lymphatic outflow (the neck veins). We tested the hypothesis that other factors besides increased neck vein pressure may cause increased lymphatic pressure during intravenous infusions. We placed cannulas into postnodal lymphatic vessels in eight sheep. After the sheep recovered from the surgery, we infused Ringer solution [46 +/- 21 (SD) ml/kg body wt in 30 min] intravenously into the sheep and inflated a balloon in the inferior vena cava. We adjusted the balloon inflation to prevent any increase in neck vein pressure during the infusions. At baseline, the intestinal lymphatic pressure was 15.5 +/- 2.5 cmH2O. During the infusions, lymphatic pressure increased significantly, and for the last 10 min of the infusion period, intestinal lymphatic pressure was 24.0 +/- 6.1 cmH2O. These results are consistent with the hypothesis that factors in addition to increased neck vein pressure may cause increased intestinal lymphatic pressure during rapid intravenous infusions.
Dissociation between plasma and brain amino acid profiles and short-term food intake in the rat
Authors: Anderson G. H. , Li E. T. , Anthony S. P. , Ng L. T. , Bialik R.
Published: December 2017

The relationship between plasma and brain amino acids and short-term food intake after administration of albumin, or its constituent amino acids, was examined. Rats given protein (0.85 g chicken egg albumin) or an amino acid mixture patterned after egg albumin reduced their food intake during 1 h of feeding beginning 30 min after gavage. Similarly, when given separately, the essential (EAA) and nonessential amino acid (NEAA) fractions of egg albumin caused comparable decreases in food intake. As the dose increased from 0.5 to 1.5 g the duration of anorexia prolonged to 12 h. Little change occurred in plasma amino acids at 30 and 60 min after albumin at 0.85 g, although many increased by 25-50% at 60 min after 1.5 g. Marked changes in plasma occurred after gavage with the total mixture of constituent free amino acids and after either EAA or NEAA fractions. Brain amino acid concentrations were little affected by albumin and did not show consistent changes after the amino acid treatments. Thus the reductions in food intake after ingestion of albumin or of its constituent amino acids were not predicted from the resulting changes in either plasma or brain concentrations of amino acids.
Anorectic responses to dietary amino acid imbalance: effects of vagotomy and tropisetron
Authors: Washburn B. S. , Jiang J. C. , Cummings S. L. , Dixon K. , Gietzen D. W.
Published: December 2017

We investigated the roles of the vagus nerve and the serotonin3 (5-HT3) receptor in mediating the food intake depression associated with amino acid deficiency. The food intake of sham-operated (sham) rats given an isoleucine-imbalanced (IMB) diet was reduced to < 40% of control basal (BAS) diet intake (P = 0.0009), and pretreatment with the 5-HT3 antagonist tropisetron (Trop) increased IMB intake by twofold over the vehicle (VEH)-treated group (P < or = 0.0001), as we have reported before. However, after subdiaphragmatic vagotomy (VAGX), IMB intake was increased to a level intermediate between the sham-VEH and sham-Trop groups, while administration of Trop did not increase IMB intake over VAGX alone. By the end of day 1, the VAGX-Trop group had eaten only 1 g more of IMB than the VAGX-VEH group (NS). We conclude that 1) the vagus is among the physiological systems involved in the anorectic responses to IMB and 2) intact vagal function is necessary for the full effect of 5-HT3 antagonists in alleviating the anorectic responses to IMB.
Factors influencing compensatory feeding during parenteral nutrition in rats
Authors: Beverly J. L. , Yang Z. J. , Meguid M. M.
Published: December 2017

During parenteral nutrition (PN) there is an incomplete compensatory decrease in oral caloric intake. The effects of two factors influencing nutrient utilization, diurnal timing of PN infusion and composition of available diet, on compensatory feeding were investigated in male rats receiving 100% of daily caloric need as PN (PN-100). Compensation for infused calories increased from 70 to 80% (P < 0.05) when the timing of infused kilocalories more closely matched diurnal pattern of oral kilocalories intake (e.g., 75% kcal daily during the dark phase, 25% during the light phase). There was a similar degree of compensation when the diet and PN-100 had the same caloric distribution (50% kcal from carbohydrate, 30% from fat, and 20% from protein). Adjusting the diurnal timing of infused calories and diet composition concurrently further increased compensation for infused calories from 70 to 90% (P < 0.05). In the rat PN-100 model, compensation for infused calories is improved by adjusting the temporal pattern of infusions and diet composition.
Angiotensin II receptors in SFO but not in OVLT mediate isoproterenol-induced thirst
Authors: Fitts D. A.
Published: December 2017

Thirst elicited by the beta-adrenergic agonist isoproterenol in rats depends in part on the secretion of renin, the consequent synthesis of angiotensin II (ANG II), and the binding of circulating ANG II to dipsogenic receptors in the brain. These receptors probably reside in either of two forebrain circumventricular organs, the subfornical organ (SFO) or organum vasculosum laminae terminalis (OVLT). Experiments determined that lesions of the SFO, but not of the OVLT, reduced drinking induced by isoproterenol treatment. Competitive ANG II-receptor antagonism with sarthran reduced isoproterenol-induced drinking when the blocker was infused into the SFO but not when it was infused into the OVLT or into the lateral ventricles at a 25-fold greater dose. The findings confirm the widely held belief that renin-dependent thirst elicited by isoproterenol relies on ANG II binding to receptor sites at a circumventricular organ in the brain. The results demonstrate that this site is the SFO and not the OVLT.
Cardiovascular reflexes during abdominal ischemia in cats
Authors: Huang H. S. , Longhurst J. C.
Published: December 2017

The cardiovascular effects of regional abdominal ischemia and reperfusion were studied in cats anesthetized with alpha-chloralose. In group 1 (n = 9), central venous pressure was kept constant by a servo-controller while the celiac and superior mesenteric arteries were occluded by loop snares for 10 min. In group 2 (n = 9), a constant-perfusion circuit to the celiac and superior mesenteric arteries that could divert flow to the femoral vein was used to induce abdominal ischemia. In group 3 (n = 7), venous return from the inferior vena cava was controlled, and a constant-perfusion circuit was used to induce abdominal ischemia. Abdominal ischemia significantly (P < 0.05) increased portal venous blood lactate from 4.3 +/- 0.6 to 6.0 +/- 0.6 mM in group 3. The early increases in blood pressure caused by passive volume shifts in groups 1 and 2 were abolished in group 3. The late, i.e., 10 min, response to abdominal ischemia consisted of significant (P < 0.05) increases in mean arterial pressure (29 +/- 7, 24 +/- 7, and 33 +/- 8 mmHg in groups 1, 2, and 3, respectively). Abdominal ischemia also significantly (P < 0.05) increased the first derivative of left ventricular pressure at 40 mmHg developed pressure from 4,355 +/- 377 to 4,839 +/- 407 mmHg/s in group 3. Celiac and superior mesenteric ganglionectomy abolished the late but not the early hemodynamic changes. Ganglionectomy also significantly (P < 0.05) enhanced the decrease in mean arterial pressure during reperfusion in all groups. We conclude that the pressor and contractile responses during 10 min of abdominal ischemia and the relative maintenance of blood pressure during reperfusion after ischemia are reflex in nature.