bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressor response from rostral dorsomedial medulla is mediated by excitatory amino acid receptors in rostral VLM
Authors: Hirooka Y. , Polson J. W. , Dampney R. A.
Published: December 2017

Excitatory amino acid (EAA) receptors in the rostral part of the ventrolateral medulla (VLM) have been shown to mediate pressor responses elicited by stimulation of various peripheral afferent fibers as well as other central nuclei. This study tested the hypothesis that these receptors are a critical component in the central pathway mediating the powerful pressor response that is produced by stimulation of a group of neurons within a circumscribed region in the rostral dorsomedial medulla (RDM). In anesthetized rabbits, the pressor response elicited by unilateral microinjection of glutamate into this RDM region was measured before and after injection of kynurenic acid (Kyn), a broad-spectrum EAA receptor antagonist, into the physiologically identified pressor region of either the ipsilateral or contralateral rostral VLM. The pressor response to RDM stimulation was greatly reduced (to 24 +/- 4% of control) 5-10 min after injection of Kyn (but not the vehicle solution) into the ipsilateral rostral VLM; this response returned completely to its control value within 30-60 min after Kyn injection. By contrast, after Kyn injection into the contralateral rostral VLM, the pressor response to RDM stimulation was not affected (106 +/- 15% of control). The results indicate that the descending pressor pathway from the RDM to the spinal cord is mediated by EAA receptors in the rostral VLM pressor region. Furthermore, the pathway from the RDM to the rostral VLM is predominantly, if not exclusively, ipsilateral.
Corticotropin-releasing hormone but not glutamate elicits hormonal responses from the parabrachial region in cats
Authors: Carlson D. E. , Nabavian A. M. , Gann D. S.
Published: December 2017

Corticotropin-releasing hormone (CRH)-containing processes were found by immunohistochemistry in the dorsal and lateral parabrachial nucleus extending medially over the dorsal aspect of the brachium and then along the lateral and medial aspects of the mesencephalic trigeminal tract. Reactivity of lesser density extended ventrally from the medial parabrachial nucleus into the locus ceruleus and subceruleus. To determine if CRH acts in these areas to modulate plasma adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP), acutely prepared, chloralose-anesthetized cats were tested with microinjections (100 nl/min, 2 min). Plasma ACTH increased significantly after injections of CRH (2 pmol) along the dorsal aspect of the brachium and in the locus subceruleus (P < 0.05 and P < 0.01, respectively). Plasma AVP increased significantly after injections of CRH into the medial parabrachial nucleus (P < 0.01). These responses of ACTH and AVP differed significantly from those to injections of either vehicle or glutamate at identical sites and from those to CRH injected in other areas. None of these latter responses was significant. CRH was without effect on arterial pressure even though glutamate (30 nmol) injected into the area ventral and medial to the brachium elicited a significant pressor response. We suggest that excitatory amino acids such as glutamate act in this area to activate neurons with descending projections that influence autonomic function. In contrast, CRH appears to activate other neurons with ascending projections that drive neuroendocrine release.
Phosphaturic effect of parathyroid hormone in the spontaneously hypertensive rat
Authors: Onsgard-Meyer M. J. , Berndt T. J. , Khraibi A. A. , Knox F. G.
Published: December 2017

The Okamoto spontaneously hypertensive rat (SHR) has been reported to have altered phosphate metabolism. Hypophosphaturia in the presence of increased serum parathyroid hormone (PTH) levels has been reported in the SHR. Therefore it has been postulated that the SHR may be hyporesponsive to the phosphaturic effect of endogenous PTH. In addition, the SHR exhibits enhanced renal sympathetic nerve activity. Recent studies demonstrated that stimulation of the renal adrenoreceptors decreases the phosphaturic response to PTH infusion. Thus a hyporesponsiveness to PTH in the SHR may be due in part to higher renal sympathetic tone. The present study determined the phosphaturic effect of a pharmacological dose of PTH (33 U/kg bolus and 1 U.kg-1.min-1 infusion) in the thyroparathyroidectomized SHR compared with its normotensive control, the Wistar Kyoto (WKY) rat. Three groups of clearance experiments were performed on male 10- to 14-wk-old SHR and WKY rats. In the first group of rats, the fractional excretion of phosphate (FEPi) in response to PTH infusion was 35.4 +/- 4.2% in the SHR (n = 6) and 26.2 +/- 3.0% in the WKY rat (n = 6), NS. In the second group, all animals underwent acute unilateral renal denervation (DNX). The FEPi in response to PTH was 35.3 +/- 1.5% in the innervated (INN) kidney of the SHR (n = 10) compared with 27.9 +/- 2.5% in the INN kidney of the WKY rat (n = 11), and 39.1 +/- 1.9% in the DNX kidney of the SHR compared with 30.5 +/- 2.0% in the DNX kidney of the WKY rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Systemic and regional hemodynamics after nitric oxide synthase inhibition: role of a neurogenic mechanism
Authors: Huang M. , Leblanc M. L. , Hester R. L.
Published: December 2017

The study tested the hypothesis that the increase in blood pressure and decrease in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control blood pressure was measured for 30 min. Cardiac output and tissue flows were measured with radioactive microspheres. All measurements of pressure and flows were made before and after NO synthase inhibition (20 mg/kg L-NAME) in a group of control animals and in a second group of animals in which the autonomic nervous system was blocked by 20 mg/kg hexamethonium. In this group of animals, an intravenous infusion of norepinephrine (20-140 ng/min) was used to maintain normal blood pressure. L-NAME treatment resulted in a significant increase in mean arterial pressure in both groups. L-NAME treatment decreased cardiac output approximately 50% in both the intact and autonomic blocked animals (P < 0.05). Autonomic blockade alone had no effect on tissue flows. L-NAME treatment caused a significant decrease in renal, hepatic artery, stomach, intestinal, and testicular blood flow in both groups. These results demonstrate that the increase in blood pressure and decreases in cardiac output and tissue flows after L-NAME treatment are not dependent on a neurogenic mechanism.
N-methyl-D-aspartate induces phase shifts in circadian rhythm of neuronal activity of rat SCN in vitro
Authors: Shibata S. , Watanabe A. , Hamada T. , Ono M. , Watanabe S.
Published: December 2017

The suprachiasmatic nucleus (SCN) acts as a pacemaker for mammalian circadian rhythms. Receptors for excitatory amino acids like N-methyl-D-aspartate (NMDA) and non-NMDA receptors have both been found to play an important role in the transmission of photic information from the retina to the SCN. Therefore, we investigated whether the application of glutamate receptor agonists could reset the phase of the circadian rhythm of SCN firing activity in vitro. Treatment with NMDA (0.1-10 microM) for 15 min or 1 h during the early part of the subjective night produced phase delay, whereas treatment during the late subjective night caused an advance in phase. The phase-response curve for NMDA was similar to that previously obtained in response to light pulses in vivo. Application of DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) (1 or 10 microM), a non-NMDA-receptor agonist, also produced a dose-dependent phase delay of SCN activity. The NMDA-induced phase delay was antagonized by an NMDA-receptor antagonist MK-801. These findings suggest that both NMDA and non-NMDA receptors may be involved in the transmission of information to the SCN via the retinohypothalamic tract. In addition, both the advances and delays in phase caused by NMDA were potentiated by cotreatment with neuropeptide Y, whereas AMPA-induced phase delay was not potentiated by neuropeptide Y. This points to a functional link between NMDA and neuropeptide Y receptor-mediated mechanisms in the SCN.
Reduced renal sympathoinhibition in response to acute volume expansion in diabetic rats
Authors: Patel K. P. , Zhang P. L.
Published: December 2017

To determine whether the renal sympathetic nerve responses to acute volume expansion (VE) are altered in the diabetic state, we measured the acute VE-induced renal sympathoinhibition in streptozotocin (STZ)-induced diabetic rats. Urine flow, sodium excretion, and integrated renal sympathetic nerve activity were measured before and during an acute graded VE (with isotonic saline) in anesthetized (Inactin; 0.1 g/kg ip) control rats (vehicle; n = 7), diabetic rats (Sprague-Dawley rats injected with STZ 65 mg/kg ip 2 wk before experiment; n = 7), and diabetic rats treated with insulin (2 U/day sc; n = 6). Blood glucose levels were significantly elevated in the diabetic group (370 +/- 8 mg/dl) compared with the control group (104 +/- 3 mg/dl). Acute graded VE with isotonic saline produced a significantly blunted renal sympathoinhibition (50% of control by 10% VE), diuresis (19% of control by 10% VE), and natriuresis (24% of control by 10% VE) in the diabetic rats compared with control rats. Treatment with insulin for 2 wk to restore normoglycemia in diabetic rats (third group; 93 +/- 9 mg/dl) resulted in reversal of the blunted urine flow, sodium excretion, and renal sympathoinhibition in response to acute VE. However, acute (a few hours before VE challenge) reduction of hyperglycemia in the diabetic rats (125 +/- 18 mg/dl) did not correct the blunted renal sympathoinhibition. The second goal of this study was to determine if enalapril treatment (10 mg/day by mouth) for 2 wk corrects the blunted volume reflex in diabetic rats. Enalapril did not correct the blunted renal excretory and renal nerve responses to acute VE in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of atrial natriuretic factor release by endothelin in ovine fetuses
Authors: Cheung C. Y.
Published: December 2017

Endothelin is a potent vasoconstrictor synthesized by vascular endothelial cells. In the adult, endothelin has been shown to stimulate the release of atrial natriuretic factor (ANF) through a direct action on atrial cardiocytes. The present study was designed to investigate, in the fetus, whether endothelin would similarly release ANF into the circulation. In addition, the effects of endothelin on fetal cardiovascular and urinary functions were explored. Chronically catheterized ovine fetuses between 126 and 139 days gestation (term 147 days) were used for the study. After a 30-min control period, the fetuses were infused intravenously with vehicle (n = 6) or endothelin-1 (n = 9) at 25 ng.min-1.kg-1 for 30 min, and this was followed by a 60-min recovery period. In response to endothelin infusion, plasma ANF levels were significantly elevated. Endothelin infusion acutely increased fetal arterial pressure without affecting venous pressure. Fetal heart rate decreased, and blood volume was reduced. Fetal urine flow rate and urinary excretion of electrolytes did not change during the endothelin infusion but were elevated during the recovery period. The fetus developed hypoxia and acidemia. Thus our study demonstrates that endothelin is effective in stimulating ANF release in the fetus, and this effect appears to be unrelated to the venous pressure changes. In addition, the results suggest that endothelin is a potent vasoconstrictor of the fetal systemic and umbilical vascular beds. The decrease in blood volume and increase in urinary excretion of fluid and electrolytes in response to endothelin are consistent with the known actions of ANF, which is elevated during endothelin infusion.
Exercise-induced 31P-NMR metabolic response of human wrist flexor muscles during partial neuromuscular blockade
Authors: Mizuno M. , Horn A. , Secher N. H. , Quistorff B.
Published: December 2017

The effects of a depolarizing (decamethonium, DECA) and a nondepolarizing neuromuscular blocking agent (vecuronium, VECU) on the phosphorus-31 nuclear magnetic resonance (31P-NMR)-detected metabolic response to muscle contractions were studied separately in six healthy untrained males. Subjects who showed splitting of the P(i) peak during graded rhythmic forearm exercise without the drugs were selected. It was found that both drugs abolished the P(i) peak splitting during exercise. Despite a similar reduction in phosphocreatine (PCr) during exercise with each drug, a smaller increase in P(i) was observed with DECA than with VECU (P < 0.05). End-exercise muscle pH was higher with DECA (6.93 +/- 0.07) than with VECU (6.79 +/- 0.11) (P < 0.05). The PCr and P(i) recovery was two- and threefold faster with DECA than with VECU, respectively (P < 0.05). On the basis of the concept that depolarizing and nondepolarizing agents have a preferential effect on fast- and slow-twitch muscle fibers, respectively, the present results support the hypothesis that the NMR-observed splitting of the P(i) peak reflects the metabolic differences between the two major fiber types of human skeletal muscle.
Role of the pons in the carotid sympathetic chemoreflex
Authors: Koshiya N. , Guyenet P. G.
Published: December 2017

The mass discharges of the splanchnic sympathetic (SND) and phrenic nerves (PND) were recorded in urethananesthetized rats with resected vagal and aortic nerves. Carotid chemoreceptor (CC) stimulation with N2 inhalation (4-12 s) or cyanide (50-100 micrograms/kg iv) activated SND in bursts synchronized with the postinspiratory phase (mean SND increase: 105 +/- 8%), raised AP, and increased PND rate and amplitude (n = 40). Brain transection at superior collicular level produced no effect. The sympathetic (SChR) and respiratory chemoreflexes (RChR) were reduced after transections through the pons. Lesions of the dorsolateral pons (dl-pons) produced CO2-dependent apneusis and/or tachypnea at rest. After such lesions, CC stimulation produced expiratory apnea and a 30% increase in SChR due to tonic activation of SND. In contrast, bilateral lesions of the ventrolateral pons (vl-pons) reduced the SChR by 54-76%. Muscimol (Mus) injections (bilateral, 175 pmol/side) into vl-pons did not change resting SND, MAP, baroreflex, and RChR but reduced the SChR (54-82%). In conclusion, under anesthesia: 1) the pathway of the carotid chemoreflex is confined to the pons and medulla, 2) the dl-pons exerts indirect control over the SChR via its role in respiratory rhythmogenesis, and 3) neurons in the vl-pons contribute selectively to the SChR but not to PND activation during CC activation.
What is responsible for the diurnal variation in potassium excretion?
Authors: Steele A. , deVeber H. , Quaggin S. E. , Scheich A. , Ethier J. , Halperin M. L.
Published: December 2017

Potassium excretion exhibits a diurnal pattern, with most excretion occurring close to noon in humans. Each component of the K+ excretion rate [urinary K+ concentration ([K+]) and flow rate] was measured and back-calculated to reflect events in the cortical collecting duct (CCD). Our purpose was to determine to what extent each component contributed to this diurnal variation in each 2-h portion of the day. In humans, K+ excretion rose threefold from nadir (0600 h) to peak (1200-1400 h), 18 h after the principal intake of K+. The variation in K+ excretion was due almost exclusively to changes in [K+] in the terminal CCD ([K+]CCD) rather than via changes in flow rate. In rats, the bulk of K+ excretion occurred shortly after eating. Both components of K+ excretion rose after meals; the rise in the [K+]CCD (3.3-fold) predominated at earlier times, and the rise in flow rate occurred later and was primarily a result of a higher rate of excretion of urea. The rise in [K+]CCD did not correlate with aldosterone levels or administration. A very large rise in the [K+]CCD only occurred in the presence of bicarbonaturia; the transtubular potassium concentration gradient was now close to 15 in the morning and evening.
L-ethionine, an amino acid analogue, stimulates eating in rats
Authors: Rawson N. E. , Ulrich P. M. , Friedman M. I.
Published: December 2017

The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) triggers feeding in rats through its actions in liver, which include a decrease in ATP due to trapping of phosphate. To determine whether decreasing liver ATP by a different means would also trigger feeding, we gave rats L-ethionine (ETH), an amino acid analogue that reduces ATP in liver by trapping adenosine as S-adenosyl-L-ethionine. ETH-treatment increased food intake from 4 to 8 h after administration, without affecting 24-h intake. Two hours after treatment, liver ATP was 25% lower in rats given ETH than in vehicle-treated controls. Circulating fuels and liver lactate and pyruvate were not affected by ETH treatment, whereas liver glycogen was 15% lower in ETH-treated rats. These results are the first to show that an amino acid analogue elicits feeding in rats fed protein-sufficient diets. Because a decrease in liver ATP is the only common effect of ETH and 2,5-AM observed thus far, a signal related to liver ATP status may be involved in the mechanism for initiation of feeding in rats.
Cardiovascular responses to hemorrhage during acute and chronic hypoxia
Authors: Resta T. C. , Russ R. D. , Doyle M. P. , Martinez J. M. , Walker B. R.
Published: December 2017

Previous work from our laboratory had demonstrated attenuation of systemic vasoreactivity to pressor agents in rats after acute or chronic exposure to hypoxia. Therefore we hypothesized that hemorrhage of acutely hypoxic (12% O2) or chronically hypoxic (barometric pressure 380 mmHg for 3 wk) rats would deter the normal increase in total peripheral resistance (TPR) and thus decrease the ability to maintain blood pressure. Progressive hemorrhage (2% of blood volume per min) was performed under conditions of either normoxia or acute hypoxia in conscious rats. In control animals, the increase in TPR observed during normoxic hemorrhage was absent when hemorrhage was performed in acute hypoxia. Furthermore, the amount of blood removal required to achieve hypotension was reduced under conditions of acute hypoxia. In contrast, chronically hypoxic rats exhibited no difference in the threshold for hypotension between conditions of acute normoxia and hypoxia and demonstrated an increased hypotensive threshold under both normoxic and hypoxic conditions compared with control animals. We next hypothesized that the prolonged threshold for hypotension observed in chronically hypoxic rats might be due to hypoxia-induced right ventricular hypertrophy. Such ventricular hypertrophy may minimize stimulation of ventricular volume receptors thought to elicit the reflex fall in heart rate and TPR occurring in extreme underfill conditions. Therefore we compared the cardiovascular responses to hemorrhage in rats with right ventricular hypertrophy resulting from administration of monocrotaline with those from rats treated with vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of estrogen on thermoregulatory evaporation in rats exposed to heat
Authors: Baker M. A. , Dawson D. D. , Peters C. E. , Walker A. M.
Published: December 2017

The purpose of this study was to determine the effects of estrogen (E2) replacement on thermoregulation in ovariectomized rats exposed to heat. Female Sprague-Dawley rats were ovariectomized and splenectomized and implanted with a temperature-sensitive transmitter. Each rat was studied when E2 treated (after an E2 pellet implant) and untreated. Animals were divided into two groups with opposite order of treatment and were studied over a 9-wk period. Measurements of body core temperature (Tc) and evaporative water loss (EWL) were made on unrestrained animals resting at 38 degrees C air temperature. E2-treated animals increased EWL at all levels of Tc, reduced the threshold Tc for onset of saliva spreading, and regulated Tc at a lower level during heat exposure. E2 treatment elevated plasma E2 and reduced hematocrit but did not affect plasma osmolality. These effects of E2 on evaporative cooling and Tc in heat-stressed rats are similar to those that have been reported in human females. The mechanisms of the thermoregulatory effects of E2 remain to be studied.
Serotonergic activity is depressed in the ventromedial hypothalamic nucleus of 12-day-old obese Zucker rats
Authors: Routh V. H. , Stern J. S. , Horwitz B. A.
Published: December 2017

We previously reported lower ventromedial hypothalamic nucleus (VMN) serotonergic activity in 11-wk genetically obese vs. lean Zucker rats. To determine whether the activity was secondary to metabolic alterations associated with this established obesity (e.g., significant hyperphagia and hyperinsulinemia), we examined monoaminergic activity in various brain nuclei of 12-day lean (Fa/Fa and Fa/fa) and obese (fa/fa) rats early in the development of obesity. Obese pups had greater percent carcass fat than heterozygotes, both of which were fatter than homozygous lean rats. Obese, but not heterozygous lean, pups were hyperinsulinemic vs. Fa/Fa pups. VMN 5-hydroxy-3-indoleacetic acid levels, an index of serotonin release, were lower in obese and heterozygous than in homozygous lean pups and were not correlated with plasma insulin levels. Although monoamine differences also occurred in several other nuclei, for the most part they appeared to be unrelated to the obese genotype. We conclude that blunted VMN serotonergic activity is not secondary to the obese rat's hyperinsulinemia and may play a significant role in the development of obesity.
Calf muscle cross-sectional area and peak oxygen uptake and work rate in children and adults
Authors: Zanconato S. , Riedy G. , Cooper D. M.
Published: December 2017

It is often assumed that the inherent peak muscle metabolic capacity scales in direct proportion to muscle cross-sectional area and is the same in small and large animals (A. V. Hill. Sci. Prog. 38: 208-230, 1950). We wondered whether this relationship between size and function was true during the period of growth and development in humans. Magnetic resonance imaging (MRI) was used to determine calf muscle cross-sectional area (CSA) in 20 children (6-11 yr old, 11 boys) and in 18 adults (23-42 yr old, 10 men). Progressive cycle ergometer exercise was performed to determine peak oxygen uptake (VO2peak) and work rate (WRpeak). The scaling factor (determined by allometric analysis) relating maximal O2 uptake (VO2max) to muscle CSA for the whole sample population was 1.04 +/- 0.12 (SE), but the scaling factor relating WRpeak to muscle CSA was significantly greater (1.37 +/- 0.12). Consistent with this, VO2max/CSA was not affected by body weight, but the WRpeak/CSA increased as a function of weight both in males (P < 0.005) and females (P < 0.05). No differences in VO2max/CSA were found between children and adults. WRpeak/CSA was significantly higher in adults compared with children (P < 0.05). It appears that the inherent peak muscle metabolic capacity is smaller in children than in adults. Moreover, the coupling of muscle capacity with whole body metabolic rate changes during growth in humans.
Effect of pregnancy on pressure-volume relationships in circulation of rabbits
Authors: Humphreys P. W. , Joels N.
Published: December 2017

Mean circulatory filling pressure (MCFP) has been measured after vagally induced cardiac arrest in 11 nonpregnant and 10 near-term pregnant rabbits, anesthetized with pentobarbital sodium. MCFP was 6.1 +/- 0.4 (SD) mmHg in the nonpregnant and 7.2 +/- 0.4 mmHg in the pregnant animals. The difference of 1.1 mmHg was significant (P < 0.001). Sympathetic blockade with bretylium tosylate (10 mg/kg) reduced MCFP by 0.4 mmHg in both nonpregnant and pregnant rabbits. Vascular capacitance was examined in the two groups. Unstressed vascular volume and vascular compliance were derived from measurements of MCFP after increasing blood volume by 8 and 16% or reducing it by 8%. The unstressed vascular volumes, 33.9 +/- 3.9 (SD) ml/kg in the nonpregnant and 35.1 +/- 3.2 ml/kg in the pregnant group, were not significantly different, but compliance in the pregnant group (4.0 +/- 0.6 ml.kg-1.mmHg-1) was significantly greater than in the nonpregnant rabbits (3.4 +/- 0.6 ml.kg-1.mmHg-1) (P < 0.05). We conclude that there are changes in vascular capacitance in rabbit pregnancy, probably not related to alterations in vasomotor activity, but these are insufficient to fully compensate for the increase in blood volume, thus leading to the rise in MCFP.
Frequency characteristics of sympathetic nerve discharge in anesthetized rats
Authors: Kenney M. J.
Published: December 2017

Frequency-domain analyses were used to characterize basal sympathetic nerve discharge (SND) and to determine the relationships between the activity recorded simultaneously from sympathetic nerves in chloralose-anesthetized, baroreceptor-innervated rats. Discharges were recorded from the splanchnic, renal, and lumbar nerves. The following observations were made. 1) Approximately 65-75% of total power in SND was contained below 9 Hz in either baroreceptor-innervated rats or baroreceptor-denervated rats. 2) Coherence values relating the activity of two nerves were significantly different from zero within this frequency band. 3) The interval between the discharges of two sympathetic nerves was either frequency dependent or constant within the coherent frequency band. 4) The frequency components of SND and the relationships between the activity in two sympathetic nerves could be altered during periods of acute stress. These results suggest that the system responsible for basal SND in rats is composed of either multiple sympathetic generators or multiple filters arranged in parallel, which are capable of producing different outputs. The dynamic nature of these circuits was revealed by the changes that occurred during periods of acute stress.
Rapid effect on suckling of an oxytocin antisense oligonucleotide administered into rat supraoptic nucleus
Authors: Neumann I. , Porter D. W. , Landgraf R. , Pittman Q. J.
Published: December 2017

Suckling in the lactating rat (days 6-10 of lactation) was used to characterize the effects of intracerebral oxytocin (Oxt) antisense oligonucleotide treatment on the hypothalamo-neurohypophysial system. Vehicle, mixed bases, Oxt antisense, or vasopressin antisense oligonucleotides (2.5 micrograms/0.5 microliter each) were infused directly into the left and right supraoptic nucleus (SON), 4 h before a litter of 10 pups was allowed to suckle for 30 min. In the Oxt antisense group, there was a significant reduction in the number of milk ejection reflexes (to 34.6 +/- 4.88%, P < 0.001), as well as in the weight gain of the litter (to 18.8 +/- 6.98%, P < 0.03) compared with vehicle (100%)-, mixed base-, or vasopressin antisense-treated animals, which did not differ from each other. The time to onset of suckling, however, was unchanged. Compared with presuckling values, plasma Oxt was significantly increased in all four groups 30 min after onset of suckling (vehicle, to 325 +/- 117%; mixed bases, to 258 +/- 48.2%; vasopressin antisense, to 330 +/- 55.7%), but this increase was less pronounced in Oxt antisense-treated rats (to 157 +/- 20.5%; P < 0.05 vs. vasopressin antisense). In contrast to these changes in neuroendocrine functions during suckling, Oxt as well as vasopressin content and Oxt immunoreactivity in posterior pituitaries and the SON, respectively, did not differ among groups. Our data indicate rapid and specific effects of an Oxt antisense oligonucleotide infused into the SON on neuroendocrine, suckling-related parameters that are not due to depleted stores of Oxt in the hypothalamo-neurohypophysial system.
Role of nitric oxide in the renal hemodynamic response to a meat meal
Authors: Salazar F. J. , Alberola A. , Nakamura T. , Granger J. P.
Published: December 2017

Ingestion of a high-protein meat meal results in significant increases in renal plasma flow (RPF) and glomerular filtration rate (GFR). The mechanism involved in this hemodynamic response to the meat meal has not yet been fully elucidated. The present study was designed to test the hypothesis that nitric oxide (NO) is involved in the renal hyperemic responses to a meat meal. To test this hypothesis, renal hemodynamic response to a meat meal (10 g/kg) was determined in conscious, chronically instrumented dogs with (n = 9) and without (n = 7) an intrarenal NO synthesis inhibition with NG-nitro-L-arginine methyl ester (L-NAME, 3 micrograms.kg-1.min-1 intrarenally). Under control conditions, the meat meal resulted in significant renal hyperemia. Three hours after ingestion of the meat meal, GFR (43 +/- 3 to 59 +/- 6 ml/min) and RPF (128 +/- 10 to 160 +/- 17 ml/min) progressively increased by approximately 40 and 25%, respectively. In contrast, pretreatment with intrarenal infusion of L-NAME abolished the GFR (48 +/- 6 to 52 +/- 6 ml/min) and RPF (129 +/- 20 to 121 +/- 17 ml/min) increases induced by the meat meal. Pretreatment with L-arginine (0.5 mg.kg-1.min-1) plus L-NAME (3 micrograms.kg-1.min-1) did not modify the meat meal-induced changes in GFR (41 +/- 4 to 66 +/- 6 ml/min) and RPF (127 +/- 9 to 182 +/- 14 ml/min). In summary, a meat meal in dogs results in marked increases in RPF and GFR. Intrarenal NO synthesis inhibition abolished the RPF and GFR responses to the meat meal.(ABSTRACT TRUNCATED AT 250 WORDS)
Exercise physiology of wild and random-bred laboratory house mice and their reciprocal hybrids
Authors: Dohm M. R. , Richardson C. S. , Garland T.
Published: December 2017

We conducted a "common garden" experiment to compare aspects of exercise physiology and voluntary wheel-running behavior in wild and random-bred (i.e., non-inbred) laboratory house mice and their reciprocal crosses. Analysis of covariance indicated that, after effects of body mass and other appropriate covariates (e.g., age at testing) were accounted for, wild (range 2.46-3.30 m/s, n = 12) and hybrid (range 1.69-3.30 m/s, n = 24) mice exhibited forced maximal sprint running speeds that averaged approximately 50% higher than those of random-bred laboratory mice (range 1.11-2.12 m/s, n = 19). Wild and hybrid mice also had significantly higher (+22%) mass-corrected maximal rates of oxygen consumption (VO2max) during forced exercise and greater (+12%) relative ventricle masses than lab mice. Wild and hybrid mice also showed statistically higher swimming endurance times relative to body mass than lab mice, although these differences were insignificant when body mass was not used as a covariate. No significant differences were found for relative gastrocnemius muscle mass, liver mass, hematocrit, or blood hemoglobin content. During a 7-day test on voluntary activity wheels, both wild and hybrid mice ran significantly more total revolutions (+101%), ran at higher average velocities when they were active (+69%), and exhibited higher maximum revolutions in any single 1-min period (+41% on the 7th day of testing), but the total number of active 1-min intervals did not differ significantly among groups. In general, the behavioral and/or whole organisms performance traits showed greater differences than the lower-level traits; thus, during the domestication of house mice, behavior may have evolved more rapidly than physiology.
Initiation of rat vasopressin cell responses to simulated hypotensive hemorrhage
Authors: Khanna S. , Sibbald J. R. , Smith D. W. , Day T. A.
Published: December 2017

Hypotensive hemorrhage is a major stimulus for vasopressin (VP) release, but in rats it is uncertain which receptors initiate this response. We have investigated this issue using transient occlusion of the inferior vena cava to simulate hypotensive hemorrhage. Single-unit recording experiments done in the supraoptic nucleus of pentobarbital-anesthetized rats demonstrated that severe caval occlusion, sufficient to drop mean arterial pressure (MAP) below 30 mmHg, excited 88% of putative VP neurosecretory cells and a similar proportion of putative oxytocin (OT) cells. Responsive VP cells increased their firing by 8.5 +/- 0.6 spikes/s within 11.2 +/- 0.8 s of the fall in MAP. This response was unrelated to the size of the fall in MAP and was unchanged by combined sinoaortic denervation (SAD) and vagal denervation, by T1 spinal section, or by administration of the angiotensin-converting enzyme inhibitor captopril, except that spinal section decreased the response latency. Moderate caval occlusion, sufficient to drop MAP to approximately 50 mmHg, did not excite any of the OT cells tested but did excite 65% of VP cells, causing a 3.8 +/- 0.3 spikes/s increase in firing after a delay of 9.0 +/- 1.3 s. This response was proportional to the size of the preceding fall in MAP, and after combined SAD and vagal denervation only 20% of VP cells still responded. Elimination of sinoaortic or vagal afferents alone had no effect on VP cell responses to moderate caval occlusion, except that SAD significantly increased the response latency. These data suggest that in rat the mechanisms that initiate the VP response to hypotensive hemorrhage depend on stimulus intensity.(ABSTRACT TRUNCATED AT 250 WORDS)
Bridging the gap between physiology and molecular biology: new approaches to perpetual questions
Authors: Norwood V. F. , Gomez R. A.
Published: December 2017

Living organisms are the result of precise and complex associations of regulatory systems in which active biomolecules interact with one another and respond to the challenges of growth and development, alterations in the environment, and disease. Understanding of body homeostasis may be accomplished at various levels of scientific endeavor. Physiological research has brought about an enormous understanding of the fundamental principles that sustain life in health and disease. The field of molecular biology has provided new tools and strategies with which to examine physiological processes as viewed from the level of fundamental biomolecules. The integration of both fields as "molecular physiology" has provided the opportunity for another level of scientific understanding and the opening of new avenues of research. Renin is one such molecule that participates in the control of several diverse physiological responses including changes in blood pressure, fluid and electrolyte homeostasis, renal function, and perhaps some elements of growth and differentiation. Because of the authors' bias, this review article will use renin to introduce many of the techniques of molecular biology and illustrate the areas of ongoing and potential interdependent activities resulting in the emerging field of molecular physiology.
Differential drives from rostral ventrolateral medullary neurons to three identified sympathetic outflows
Authors: McAllen R. M. , May C. N.
Published: December 2017

Simultaneous recordings were made in chloralose-anesthetized cats from muscle vasoconstrictor (MVC), visceral vasoconstrictor (VVC), and renal (RSN) sympathetic fibers. Their barosensitivity was demonstrated, after which all baroreceptor nerves were cut. Multiple microinjections of sodium glutamate (5 nl, 0.1 M) were made in a grid pattern covering the rostral ventrolateral medulla (RVLM) pressor area on seven sides of four animals. Injections increased blood pressure by up to 87 +/- 22 mmHg and MVC, VVC, and RSN activities by up to 169 +/- 55, 62 +/- 23, and 67 +/- 36%, respectively. The relative responses between nerves (taken in pairs) showed significant inhomogeneity across injections into 5/7, 6/7, and 1/7 RVLMs for MVC vs. VVC, MVC vs. RSN, and VVC vs. RSN, respectively. Calculation showed that overall, less than half the response spikes due to RVLM glutamate injections could be accounted for by a hypothetical population of neurons that excited MVC, VVC, and RSN outflows in fixed proportion. Sites that exclusively drove MVC, VVC, or RSN outflows were found in 7/7, 3/7, and 5/7 RVLMs, respectively. Sites that selectively drove either nerve of a given pair were ubiquitous. The RVLM territories from which the three outflows could be activated overlapped but showed clear differences. Their shapes and sizes differed between animals and even between sides. They covered the subretrofacial (SRF) nucleus plus a variable rostromedial extension. The data support the view that the RVLM neurons driving these three sympathetic outflows are largely, perhaps entirely, separate populations.
Relationship between strength of short-term systemic autoregulation and initial resistance
Authors: Burattini R. , Borgdorff P. , Westerhof N.
Published: December 2017

The relationship between strength of short-term whole body autoregulation and peripheral resistance in the reference state (initial resistance) was investigated in 9 anesthetized closed-chest dogs and 18 anesthetized open-chest cats. Baroreflex regulation was abolished in one of three ways: barodenervation, ganglionic blockade, or setting pressure constant in the isolated carotid sinuses after vagotomy. Ascending aortic pressure and flow and venous pressure were measured in the reference state and 1-3 min after partial occlusions of the inferior vena cava. Cardiac output and peripheral resistance (ratio between arteriovenous pressure difference and cardiac output) were normalized for body weight. Strength of autoregulation was quantified by a resistance gain (Gra), defined as the ratio between change in normalized peripheral resistance and corresponding change in normalized cardiac output. A broad range of values for peripheral resistance in the reference state (Ro) was obtained as a result of the different interventions used to abolish baroreflex regulation. Arteriovenous pressure difference and normalized cardiac output during multiple vena cava occlusions in the 9 dogs and in 8 of the cats were fitted with a parabola convex to the flow axis. From the best fit, Gra was estimated. In the remaining 10 cats Gra was estimated from a single occlusion of vena cava. When data of all dogs and cats were taken together, we found a linear relationship between Gra and Ro: Gra = K1.Ro + K2. The constants K1 and K2 were 17.9 x 10(-3) min.kg.ml-1 and -14.5 x 10(-3) mmHg.min2.kg2.ml-2, respectively. The correlation coefficient was 0.9.
Circadian and estrous cycle-dependent variations in blood pressure and heart rate in female rats
Authors: Takezawa H. , Hayashi H. , Sano H. , Saito H. , Ebihara S.
Published: December 2017

To determine whether cardiovascular functions are controlled by the endogenous circadian system and whether they change with the estrous cycle in female rats, we measured mean arterial pressure (MAP), heart rate (HR), and spontaneous activity (ACT) of female rats using an implantable radiotelemetry device and a computerized data-collecting system. Under a 12:12-h light-dark (LD) cycle, these parameters exhibited daily rhythms that were entrained to the photic cycle. The patterns of the daily rhythms varied with estrous cycles, and variations were particularly marked in the proestrous stage. During the dark period of this stage, ACT levels were significantly higher, but HR was significantly lower than in other stages. Although the peak MAP occurred within 2 h after the onset of the dark phase in three of the estrous stages, it occurred around midnight in the proestrous stage. Such estrous cycle-dependent variations were eliminated by ovariectomy. The implantation of 17 beta-estradiol produced a gradual increase in MAP and an abrupt decrease in HR. During constant darkness, all three parameters were free running, maintaining the same internal phase relationships with each other as during LD cycles. These results indicate that daily variations in these parameters were controlled by the endogenous circadian oscillating system, that they vary with the estrous cycle in female rats, and that estrogen may be responsible for these estrous cycle-dependent variations.
Sodium deprivation blunts hypovolemia-induced pituitary secretion of vasopressin and oxytocin in rats
Authors: Stricker E. M. , Schreihofer A. M. , Verbalis J. G.
Published: December 2017

The present investigations determined the effects of dietary sodium deprivation on the neurohypophysial secretion of arginine vasopressin (AVP) and oxytocin (OT) by rats in response to nonhypotensive hypovolemia induced by subcutaneous injection of 30% polyethylene glycol solution. In rats fed either standard sodium-rich laboratory chow or sodium-deficient diet for 8 days, AVP secretion increased gradually in proportion to plasma volume deficits up to 22-28% while pituitary secretion of OT was not stimulated. However, when hypovolemia was more pronounced, secretion of both hormones was marked in rats fed standard chow, whereas rats fed sodium-deficient diet were significantly less responsive. These effects did not reflect a general insensitivity of the neurohypophysial system because sodium-deprived and chow-fed rats secreted AVP and OT equivalently in response to intravenous infusion of 1.5 M NaCl solution. Nor did they reflect a general insensitivity to hypovolemia because sodium-deprived rats drank substantial, above-normal volumes of water after colloid treatment. Instead, the results appear to reflect a specific inhibition of stimulatory baroreceptor inputs to AVP and OT neurons during dietary sodium deprivation in rats.
Alterations of synaptic transmission in sympathetic ganglia of spontaneously hypertensive rats
Authors: Magee J. C. , Schofield G. G.
Published: December 2017

An enhanced sympathetic nerve activity (SNA) has been implicated in the development and maintenance of the hypertension observed in experimental animal models such as the spontaneously hypertensive rat (SHR). Recent evidence suggests that an alteration of sympathetic synaptic transmission could also play a significant role in the elevation of SNA observed in the SHR (J. C. Magee and G. G. Schofield. Hypertension Dallas 20: 367-373, 1992). To test this hypothesis, we used intracellular recordings from superior cervical ganglion (SCG) neurons to compare properties of synaptic transmission between SHRs and two normotensive controls [Wistar-Kyoto (WKY) and Wistar rats]. Supramaximal preganglionic stimulation elicited larger amplitude fast excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) in SHR sympathetic neurons compared with the normotensive controls. Analysis of variance of both compound and unitary EPSC amplitudes suggests that an increase in transmitter release is responsible for the elevated EPSP amplitude in these neurons. Also, a diminished short-term facilitation and an elevated synaptic depression limit the ability of SHR preganglionic neurons to increase transmitter release during short trains of repetitive stimuli. It is hypothesized that an enhanced transmitter depletion results in the altered synaptic plasticity of SHR sympathetic ganglion neurons. Intracellular recordings in low-Ca2+, high-Mg2+ external solutions support this idea. Therefore, synaptic transmission between the preganglionic and postganglionic neurons of SCGs from hypertensive rats was found to be altered in a manner that would tend to enhance sympathetic nervous activity, further implicating an exaggerated SNA in the pathogenesis of hypertension in the SHR model.
Metabolic clearance of atrial natriuretic factor in ovine pregnancy
Authors: Mukaddam-Daher S. , Gutkowska J. , Nuwayhid B. S. , Quillen E. W.
Published: December 2017

Plasma atrial natriuretic factor (ANF) is normally released into the circulation primarily by volume expansion and atrial distension, but we have shown that plasma ANF is elevated in pregnant sheep before volume expansion. Because alterations in the metabolic clearance of ANF could lead to elevated plasma ANF levels, the present study was designed to determine the pharmacokinetics of plasma ANF in pregnant sheep. Chronically instrumented nonpregnant and pregnant sheep received intravenous injections of monoiodinated human ANF (125I-hANF). Plasma decay curves of 125I-hANF followed a biexponential function in both groups. High-performance liquid chromatography (HPLC) revealed the accumulation of smaller degradation products by 2 min postinjection, and by 30 min no intact ANF was present. Because HPLC identification of ANF and its metabolites was shown to be more efficient than precipitation with 10% trichloroacetic acid (TCA) or extraction by Sep-Pak cartridges, ANF kinetic parameters were calculated from HPLC-corrected plasma decay curves. Injected ANF was rapidly distributed in an initial distribution volume (IDV) that was expanded in pregnant sheep. Metabolic clearance rate (MCR) was greater in pregnant sheep (2.8 +/- 0.3 vs. 6.8 +/- 1.2 l/min, P = 0.002), while plasma half-life (t1/2) was not altered (2.2 +/- 0.5 vs. 2.4 +/- 0.4 min). The data demonstrate that during pregnancy, the t1/2 of ANF is not altered but the MCR of ANF is enhanced. These findings imply that plasma ANF is increased by mechanisms other than reduced clearance in pregnant sheep.
Tumor necrosis factor-alpha and fever after peripheral inflammation in the rat
Authors: Cooper A. L. , Brouwer S. , Turnbull A. V. , Luheshi G. N. , Hopkins S. J. , Kunkel S. L. , Rothwell N. J.
Published: December 2017

The involvement of endogenous tumor necrosis factor-alpha (TNF-alpha) in the pyrogenic [i.e., rise in colonic temperature (Tc)] and thermogenic [increase in oxygen consumption (VO2)] responses to inflammation was investigated in rats subjected to an intramuscular injection of turpentine. Turpentine administration caused a rise in Tc and VO2 within 2 h (0.9 +/- 0.1 degrees C, 27 +/- 2%, respectively). Eighteen to twenty hours after turpentine, the magnitude of these responses had increased (2.3 degrees C fever and a 28% increase in metabolic rate compared with control animals) and was associated with marked inflammation in the injected limb. A rapid (by 4 h) and sustained rise in the plasma concentration of the endogenous pyrogen IL-6, but not TNF-alpha, was also observed. Intravenous pretreatment with a TNF-alpha antiserum attenuated the rise in Tc observed 2, 8, and 18 h after turpentine injection and almost abolished the hypermetabolic response observed at 18 h. In addition, the TNF-alpha antiserum inhibited the peak rise (8 h) in plasma IL-6 by 76%. These findings indicate that endogenous TNF-alpha is involved in fever and hypermetabolism during inflammation and that it may exert these effects by inducing the release of IL-6 into circulation.
Blood and brain temperatures of free-ranging black wildebeest in their natural environment
Authors: Jessen C. , Laburn H. P. , Knight M. H. , Kuhnen G. , Goelst K. , Mitchell D.
Published: December 2017

Using miniature data loggers, we measured the temperatures of carotid blood and brain in four wildebeest (Connochaetes gnou) every 2 min for 3 wk and every 5 min, in two of the animals, for a further 6 wk. The animals ranged freely in their natural habitat, in which there was no shelter. They were subject to intense radiant heat (maximum approximately 1,000 W/m2) during the day. Arterial blood temperature showed a circadian rhythm with low amplitude (< 1 degree C) and peaked in early evening. Brain temperature was usually within 0.2 degrees C of arterial blood temperature. Above a threshold between 38.8 and 39.2 degrees C, brain temperature tended to plateau so that the animals exhibited selective brain cooling. However, selective brain cooling sometimes was absent even when blood temperature was high and present when it was low. During helicopter chases, selective brain cooling was absent, even though brain temperature was near 42 degrees C. We believe that selective brain cooling is controlled by brain temperature but is modulated by sympathetic nervous system status. In particular, selective brain cooling may be abolished by high sympathetic activity even at high brain temperatures.