bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteins and lipids define the diffusional field of nitric oxide
Authors: Porterfield D. Marshall , Laskin Jeffrey D. , Jung Sung-Kwon , Malchow Robert Paul , Billack Blase , Smith Peter J. S. , Heck Diane E.
Published: December 2017

Nitric oxide (NO) fluxes released from the surface of individual activated macrophages or cells localized in small aggregates were measured with a novel polarographic self-referencing microsensor. NO fluxes could be detected at distances from the cells of 100–500 μm. The initial flux and the distance from the cells at which NO could be detected were directly related to the number of cells in the immediate vicinity of the probe releasing NO. Thus, whereas NO fluxes of ∼1 pmol · cm−2· s−1were measured from individual macrophages, aggregates composed of groups of cells varying in number from 18 to 48 cells produced NO fluxes of between ∼4 and 10 pmol · cm−2· s−1. NO fluxes required the presence of l-arginine. Signals were significantly reduced by the addition of hemoglobin and by N-nitro-l-arginine methyl ester. NO fluxes were greatest when the sensor was placed immediately adjacent to cell membranes and declined as the distance from the cell increased. The NO signal was markedly reduced in the presence of the protein albumin but not by either oxidized or reduced glutathione. A reduction in the NO signal was also noted after the addition of lipid micelles to the culture medium. These results demonstrate that NO can be detected at significant distances from the cell of origin. In addition, both proteins and lipids strongly influence the net movement of free NO from macrophages. This suggests that these tissue components play an important role in regulating the biological activity of NO.
Plasma epinephrine appearance and clearance rates in fetal and newborn sheep
Authors: Stein H. , Oyama K. , Martinez A. , Chappell B. , Padbury J.
Published: December 2017

Newborn plasma catecholamine levels are elevated compared to fetal life. Whether this reflects increased catecholamine secretion after birth or decreased clearance is not known. To determine the plasma appearance and clearance rates for catecholamines during the transition to postnatal life, we compared plasma epinephrine appearance and clearance rates in fetal sheep before birth and in newborns after delivery. Plasma epinephrine appearance and clearance rates were measured by radiotracer analysis in eight fetuses at 127 +/- 1 days of gestation and, after cesarean delivery, at 130 +/- 1 days of gestation. There was no difference in plasma epinephrine appearance rate during the fetal (26 +/- 4 ng.kg-1 x min-1) or newborn studies (31 +/- 5 ng.kg-1 x min-1). The fetal plasma epinephrine clearance rate (131 +/- 13 ml.kg-1 x min-1) was significantly higher than newborn plasma epinephrine clearance rate (40 +/- 3 ml.kg-1 x min-1). Thus fetal plasma epinephrine appearance rate is not different from appearance rate in the immediate newborn period when catecholamine levels are higher than during most other physiological circumstances. The increase in circulating catecholamine levels at birth is due in part to a significant decrease in clearance rate. It is likely that removal of the placental contribution to whole body clearance accounts for much of the difference observed in fetal and newborn clearance rates.
Determinants of fasting hypertriglyceridemia in ventromedial hypothalamic obesity in rats
Authors: Inoue S. , Satoh S. , Tanaka K. , Takamura Y. , Murase T.
Published: December 2017

The present study investigated the mechanism of fasting hypertriglyceridemia in ventromedial hypothalamic (VMH) obesity by measurement of post-heparin plasma lipoprotein lipase (LPL) activity, triglyceride secretion rate (TGSR), and plasma insulin. One week after VMH lesions, when the lesioned rats were gaining weight rapidly (the dynamic phase), they showed normal plasma triglyceride levels with increased plasma LPL activity and TGSR. There was a positive correlation between hyperinsulinemia and elevated plasma LPL activity or TGSR in VMH-lesioned rats, while no correlation was observed in control rats. Ten weeks after VMH lesions, when the rats had become obese and reached a steady-state weight gain (the static phase), they showed hypertriglyceridemia with increased plasma LPL activity and TGSR. There was, again, a positive correlation between hyperinsulinemia and elevated plasma LPL activity or TGSR in VMH-lesioned rats. These results suggest a possible mechanism of fasting hypertriglyceridemia in these rats; in the dynamic phase adipose tissue adequately takes up circulating triglyceride because the tissue has sufficient take-up capacity and hence hypertriglyceridemia does not develop. In the static phase the tissue cannot adequately take up circulating triglyceride because of a limitation of its capacity, resulting in hypertriglycemia despite enhanced triglyceride secretion and increased LPL activity in both phases.
Effect of CO2/pH on the aldosterone response to hypoxia in bovine adrenal cells in vitro
Authors: Raff H. , Jankowski B.
Published: December 2017

Acidosis increases and hypoxia decreases aldosterone production from the adrenal zona glomulerosa in vivo, in situ, and in vitro. These effects appear to be located at different steps in the steroidogenic process. Because respiratory acidosis and hypoxemia are common sequelae of chronic lung disease, the present experiments evaluated the interaction of hypoxia and CO2 (with uncompensated or compensated extracellular pH) on aldosteronogenesis in vitro. Bovine adrenal zona glomerulosa cells were stimulated with angiotensin II (ANG II) or adenosine 3',5'-cyclic monophosphate under room air control (21% O2-0% CO2), CO2 per se (21% O2-10% CO2), hypoxia per se (10% O2-0% CO2), and the combination of CO2 and hypoxia (10% O2-10% CO2). Furthermore, under CO2, pH was either allowed to decrease from 7.2 to 6.8 (uncompensated) or its decrease was minimized (> 7.05) with NaOH (compensated). CO2 without pH compensation led to a significant increase in ANG II-stimulated aldosterone release; when the decrease in pH was minimized, CO2 inhibited ANG II-stimulated aldosterone release. Hypoxia inhibited aldosterone release; the inhibitory effect of hypoxia predominated when combined with CO2. In the presence of cyanoketone, pregnenolone production from endogenous precursors (early pathway) was unaffected. However, the conversion of corticosterone to aldosterone (late pathway) was inhibited by low O2 but unaffected by CO2. It is concluded that the inhibitory effect of low O2 on the late pathway predominates over the effects of uncompensated or compensated simulated respiratory acidosis on aldosteronogenesis.
Augmented glucoregulatory hormone concentrations during exhausting exercise in mildly iron-deficient rats
Authors: Zinker B. A. , Dallman P. R. , Brooks G. A.
Published: December 2017

We hypothesized that augmented responses of glucoregulatory hormones in iron deficiency would enhance liver and muscle glycogenolysis, leading to increased gluconeogenic precursor (lactate) supply and upregulation of hepatic gluconeogenesis. Female weanling rats were randomly placed on either a mildly iron-deficient (-Fe; 15 mg Fe/kg diet) or an iron-sufficient (+Fe; 50 mg Fe/kg diet) diet for 4 wk and studied at rest and during exhaustive treadmill running. Hemoglobin was 9.0 +/- 0.2 and 13.1 +/- 0.3 g/dl in -Fe and +Fe, respectively, after 3.5 wk of dietary iron deficiency. Arterial plasma epinephrine (Epi), norepinephrine (NE), adrenocorticotropic hormone (ACTH), corticosterone, insulin, and glucagon levels were similar at rest in both groups, as were liver, gastrocnemius, and superficial and deep vastus medialis glycogen levels. Liver and kidney phosphoenolpyruvate carboxykinase (PEPCK) activities were similar in both groups. Maximum O2 consumption was decreased (22%) in -Fe. Respiratory exchange ratio (CO2 production/O2 consumption) was unaffected at rest but increased at maximum O2 consumption in -Fe. Time to exhaustion during a standardized running test (13.4 m/min, 0% grade) was decreased 45% in -Fe (63 +/- 5 vs. 116 +/- 10 min). During exercise, euglycemia was maintained in both groups, but blood lactate was elevated in -Fe. The mean net glycogen utilization during exercise was increased in liver (43%), soleus (33%), and superficial vastus medialis (106%) and decreased in the gastrocnemius (36%) in -Fe. Liver and kidney PEPCK activities were increased similarly at exhaustion in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Modulation of in situ canine intrinsic cardiac neuronal activity by locally applied adenosine, ATP, or analogues
Authors: Huang M. H. , Sylven C. , Pelleg A. , Smith F. M. , Armour J. A.
Published: December 2017

To determine whether adenosine or ATP can modify mammalian intrinsic cardiac neurons, these substances, as well as their analogues 5'-(N-ethylcarboxamido)-adenosine (NECA), N6-cyclopentyladenosine (CPA), and beta,gamma-methylene ATP (beta,gamma-mATP), were applied in microliter quantities adjacent to spontaneously active canine atrial ganglionated plexus neurons in 14 anesthetized open-chest dogs. Adenosine, NECA, and CPA induced neuronal responses, neuronal activity being either increased or decreased in 81, 86, and 86% of the sites tested, respectively. Cardiovascular responses were elicited by these agents in 21-31% of neurally active loci. ATP and beta,gamma-mATP elicited neuronal responses in 100 and 70% of tested loci, respectively. Associated cardiovascular responses were elicited by ATP and beta,gamma-mATP in 35 and 18% of the sites, respectively. After acute decentralization of the intrinsic cardiac nervous system, neuronal responses were elicited by purines in 73% of the previously active sites, while cardiovascular responses were either attenuated or eliminated. It is concluded that exogenous purine nucleosides and nucleotides can modulate the activity generated by in situ intrinsic cardiac neurons presumably by acting on P1 and P2 purinoreceptors. Furthermore, these data indicate that purine sensitive intrinsic cardiac neurons are involved in cardiac regulation.
Arginine vasopressin produces renal vasodilation via V2 receptors in conscious dogs
Authors: Naitoh M. , Suzuki H. , Murakami M. , Matsumoto A. , Ichihara A. , Nakamoto H. , Yamamura Y. , Saruta T.
Published: December 2017

In conscious dogs, 36-h water deprivation induced a significant increase in renal blood flow (RBF) with elevation of the plasma arginine vasopressin (AVP) concentration to 9.6 +/- 1.8 pg/ml. To simulate such a condition, a mild elevation of plasma AVP was produced by infusing AVP intravenously at a dose of 0.1 ng.kg-1.min-1 for 20 min. The plasma AVP concentration then increased to 6.8 +/- 0.7 pg/ml. This dose of AVP increased the RBF by 21.7 +/- 2.6% and decreased the renal vascular resistance by 18.1 +/- 2.3% without significant changes in mean arterial pressure, cardiac output, or heart rate. The mechanism of this renal vasodilatory action was examined using newly developed, orally effective, selective AVP antagonists OPC-21268 (a V1-receptor antagonist) and OPC-31260 (a V2-receptor antagonist). In 36-h water-deprived dogs, V2-receptor blockade with OPC-31260 significantly decreased the RBF by 20.5 +/- 2.6% without significant changes in cardiac output. The exogenous AVP-induced renal vasodilatory response tended to be augmented when V1 receptors were blocked by pretreatment with OPC-21268, but the change did not achieve statistical significance. On the other hand, V2-receptor blockade by either pretreatment with OPC-31260 or simultaneous infusion of OPC-31260 inhibited this vasodilatory response. Furthermore, intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP) at a dose of 0.3 ng.kg-1 x min-1 for 20 min significantly increased the RBF by 36.5 +/- 1.7%, and this DDAVP-induced renal vasodilation was inhibited by simultaneous infusion of V2-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Torpor shortens the period of Siberian hamster circadian rhythms
Authors: Thomas E. M. , Jewett M. E. , Zucker I.
Published: December 2017

We investigated the influence of ambient and body temperature (Ta and Tb) on circadian rhythms of gonadectomized male Siberian hamsters. Animals that entered torpor (Tb < 30 degrees C) had significantly shorter circadian periods (tau s) than did nontorpid hamsters at a Ta of 13 degrees C (24.17 +/- 0.05 vs. 24.33 +/- 0.04 h). The tau s of homeothermic hamsters were not affected by Ta change. Short-term decreases in Tb, rather than changes in Ta, appear to affect tau. Access to activity wheels inhibited expression of torpor in short daylengths and was associated with significant increases in body mass. Running wheel activity can mask or block specific short-day responses.
Skeletal muscle as the major site of nonshivering thermogenesis in cold-acclimated ducklings
Authors: Duchamp C. , Barre H.
Published: December 2017

Despite their lack of brown adipose tissue, 6-wk-old cold-acclimated muscovy ducklings (4 degrees C; CA) exhibit nonshivering thermogenesis (NST) in the cold. To determine the site of this NST, the regional distribution of blood flow was measured by the microsphere method in the thermoneutral zone (25 degrees C) and during acute exposure to cold (8 degrees C). Ducklings reared at thermal neutrality (TN), which use shivering to produce extra heat in the cold, were compared with CA ducklings, which substitute NST for shivering. Further, the contribution of skeletal muscle thermogenesis to the increased heat production in the cold was estimated by measuring leg muscle blood flow and arteriovenous difference in oxygen content [(a-v)O2] across the leg, enabling an estimation of muscle O2 consumption. During cold exposure, a similar increase in total leg muscle blood flow occurred in TN and CA ducklings (+127 and +130% respectively), while hepatic arterial blood flow increased less (+56 to +37%, respectively). This rise in blood flow was accounted for by an increase in cardiac output, which was smaller in CA than in TN ducklings, and in both groups by a redistribution of blood flow to the most thermogenic organs (skeletal muscles and liver). The (a-v)O2 across the leg was not changed by cold exposure, indicating that the increase in leg muscle O2 consumption resulted mainly from the increase in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasticity of autonomic control of emesis in irradiated ferrets
Authors: Makale M. T. , King G. L.
Published: December 2017

To investigate the plasticity of the emetic response to irradiation, five groups of ferrets (with the appropriate controls) had either the vagal or the splanchnic nerves transected and either were immediately irradiated under urethan anesthesia or were irradiated in a conscious state at 0.5-4, 4-9, and 24 h and 7 days after nerve transection. All the ferrets used in this study had the left carotid artery and the right jugular vein catheterized several hours before irradiation so that blood pressures could be monitored. In ferrets that were irradiated while anesthetized, bilateral abdominal vagotomy performed immediately before 6-Gy irradiation prevented emesis. Acute bilateral abdominal splanchnicectomy markedly reduced emesis in such cases but had no statistically significant effect in conscious ferrets. The incidence of emesis in conscious controls laparotomized 0.5-4 h before irradiation was 50% after 2 Gy and 100% after 6 Gy. Intact conscious controls were tested with 10 Gy only and showed a 100% incidence of emesis after this dose. Bilateral abdominal vagotomy, performed on ferrets 4-9 h before 8-Gy irradiation of conscious animals, markedly reduced the incidence of radiation-induced emesis. When performed 24 h before irradiation, it abolished emesis. In contrast, vagotomy was ineffective when performed 7 days before irradiation. The data suggest that, after 2-8 Gy, the vagi are the major emetic pathway in conscious ferrets and the splanchnic nerves may, under certain conditions, constitute second or alternate pathways.
Daily intervals of heat exposure alter the phase of the daily variation of plasma hormones in Holtzman rats
Authors: De Souza C. J. , Meier A. H.
Published: December 2017

The effects of timed daily increases in ambient temperature (thermopulses) (from 22 +/- 1 to 40 +/- 1 degree C for 2 h) on daily variations of hormones involved in glucose and lipid metabolism were tested in male Holtzman rats (3-4 mo old) exposed to a 12-h daily photoperiod. The thermopulses were administered for 14 days either at light onset (TP0) or 16 h after light onset (TP16). Body weights and food consumption were monitored during the experiment. Retroperitoneal fat weights and plasma concentrations of insulin, glucose, glucagon, corticosterone, and prolactin were determined from blood taken every 4 h during a 24-h period commencing 24 h after the last thermopulse. TP0 treatment did not alter any of the parameters tested. Conversely, TP16 treatment obliterated the daily rhythms of insulin and corticosterone present in the controls (nonthermopulsed) and decreased body weight gains, retroperitoneal fat stores, food consumption, and the baseline levels of plasma insulin and corticosterone. The present study supports a role for circadian neuroendocrine rhythms in the reduction of fat stores induced by properly timed daily thermopulses.
Mechanisms underlying cardiovascular defense reaction evoked by dorsal periaqueductal gray stimulation
Authors: Watkins L. , Sherwood A. , Goldstein D. S. , Maixner W.
Published: December 2017

Hemodynamic and autonomic mechanisms underlying the cardiovascular defense reaction elicited by electrical stimulation of the dorsolateral periaqueductal gray region were evaluated in pentobarbital sodium-anesthetized Sprague-Dawley rats. Stimulation of this area produced transient increases in mean arterial pressure and more sustained increases in heart rate, hindlimb blood flow, and plasma catecholamine levels. The pressor component of the defense reaction was due entirely to increased total peripheral vascular resistance; elevations in cardiac output occurred only at the end of the stimulation period when blood pressure had returned to resting values. The hindlimb vasodilatory response included distinct early and late components. The late component was produced by epinephrine-mediated activation of beta 2-receptors because it was abolished by bilateral adrenalectomy or treatment with butoxamine, a beta 2-receptor selective antagonist. In contrast, the early component was only partially reduced by adrenalectomy or butoxamine treatment. During conditions of constant flow provided by a pump-perfused hindlimb preparation, the early hindlimb vasodilatory response was eliminated and a neurogenic vasoconstrictor response revealed. This finding suggests that the early hindlimb blood flow response may result from shunting of blood from highly vasoconstricted vascular beds to relatively less constricted hindlimb vasculature.
Effects of temperature on muscle pHi and phosphate metabolites in newts and lungless salamanders
Authors: Johnson D. C. , Burt C. T. , Perng W. C. , Hitzig B. M.
Published: December 2017

The effect of acute alterations in body temperature (BT) on intracellular pH (pHi) and phosphate metabolites was assessed in white skeletal muscle of intact newts and lungless red-backed salamanders using 31P-nuclear magnetic resonance spectroscopy. pHi decreased with increasing BT in the tail muscle of both newts and lungless red-backed salamanders. The change in pH with change in temperature from 10 to 30 degrees C was -0.018 U/degrees C in newts and -0.041 U/degrees C in red backs. The calculated alpha-imidazole for skeletal muscle cytosol did not change (0.56) in newts from 10 to 30 degrees C but fell from 0.69 to 0.43 in red-backed salamanders. Phosphocreatine (PCr)/Pi fell and Pi/beta-ATP rose with increasing temperature in both newts and red backs; however, the change was much greater in red backs. Providing the red backs with O2 at 30 degrees C led to higher pH and alpha-imidazole, comparable to that of newts, along with increased PCr/Pi and lower Pi/beta-ATP. Thus newts maintain white skeletal muscle cell cytosol alpha-imidazole constant with changes in BT, whereas red backs apparently do not. However, at the BT of preference, red backs and newts maintain similar muscle pHi and alpha-imidazole. The method of gas exchange appears to strongly influence the ability of an animal to maintain its acid-base status over a range of temperatures, and our results suggest that behavioral regulation of BT may involve alpha-imidazole regulation as well.
Tonic descending modulation of spinal neuronal responses to activation of renal receptors
Authors: Standish A. , Vizzard M. A. , Ammons W. S.
Published: December 2017

Experiments were conducted in anesthetized cats to determine if spinal neuronal responses to activation of renal receptors are tonically modulated by descending spinal pathways. Eighty-seven thoracolumbar spinal neurons with renal and somatic input were tested for responses to occlusion of the renal vein, renal artery, and ureter before, during, and after cooling the spinal cord rostral to the recording site. Cooling increased the number of neurons that responded as well as the magnitude of the responses to renal vein (RVO), renal artery (RAO), and ureteral occlusion (UO). RVO increased cell activity of 21 neurons from 12.5 +/- 2.7 to 31.7 +/- 6.0 spikes/s during cooling. UO increased cell activity of 24 neurons from 9.0 +/- 2.1 before cooling to 25.0 +/- 4.9 spikes/s during cooling. Cold block increased the magnitude of both types of responses to RAO that were due to mechanical deformation of the renal artery and prolonged renal ischemia. These data show that the majority of spinal neuronal responses to renal receptor stimulation are modulated by tonic inhibitory influences. Thus these results provide a mechanism by which the brain may control spinal circuitry that underlies reflexes of renal origin.
Dehydration tolerance in wood frogs: a new perspective on development of amphibian freeze tolerance
Authors: Churchill T. A. , Storey K. B.
Published: December 2017

Wood frogs, Rana sylvatica, tolerate the loss of 50-60% of total body water during experimental dehydration. The rate of water loss for unprotected frogs is the same whether animals are frozen (at -2 degrees C) or unfrozen (at 1 degrees C) but is greatly reduced when frogs are frozen under a protective layer of moss. Dehydrational death could occur in as little as 7-9 days for unprotected animals; this indicates the importance for winter survival of selecting well-protected and damp hibernation sites. Prior dehydration affected the cooling and freezing properties of frogs, reducing supercooling point and the amount of ice formed after 24 h at -2 degrees C and acting synergistically with freezing exposure in stimulating cryoprotectant synthesis. Analysis of the effects of controlled dehydration at 5 degrees C showed that changes in body water content alone (without freezing) stimulated liver glycogenolysis and the export of high concentrations of glucose into blood and other organs. Autumn-collected frogs dehydrated to 50% of total body water lost showed glucose levels of 165-1,409 nmol/mg protein in different organs, increases of 9- to 313-fold compared with control values and reaching final levels very similar to those induced by freezing exposure. The data support the proposal that various adaptations for natural freeze tolerance may have been derived from preexisting mechanisms for dealing with water stress in amphibians and that cell volume change may be one of the signals involved in triggering and sustaining molecular adaptations (e.g., cryoprotectant output) that support freezing survival.
NTS neuronal responses to arterial pressure and pressure changes in the rat
Authors: Rogers R. F. , Paton J. F. , Schwaber J. S.
Published: December 2017

Central representation of arterial pressure by baroreceptor target neurons in the nucleus of the solitary tract (NTS) has not been studied. The present experiments sought to characterize response patterns of NTS baroreceptive cells in anesthetized, paralyzed, and artificially ventilated rats to both resting pressures and induced blood pressure challenges. Single-unit extracellular recordings were made from 83 baroreceptive NTS cells that received a synaptic input after electrical stimulation of the aortic nerve [latency, 2.46 +/- 0.78 (+/- SD) ms] and were located at an anatomically defined region known to receive baroreceptor afferents. Seventy-one neurons were presumed second order, since they received a short (< 5 ms) and invariant (< +/- 0.5 ms) synaptic input from the ipsilateral aortic nerve. Thirty-five of these neurons were silent at resting blood pressures and produced few (1-4) spikes when presented with induced pressor responses. The remainder (n = 36) had ongoing activity that was not pulse rhythmic and that varied in rate nonuniformly with arterial blood pressure during an induced challenge. Ongoing activity was analyzed for active neurons, revealing both R wave-related and lung inflation-related phasic activity. The present data suggest that baroreceptive NTS neurons may be sensitive to many characteristics of the input signal, such as dP/dt, mean pressure, and cardiac frequency, as well as pulmonary afferent drive.
ICI 182,780: a pure antiestrogen that affects behaviors and energy balance in rats without acting in the brain
Authors: Wade G. N. , Blaustein J. D. , Gray J. M. , Meredith J. M.
Published: December 2017

ICI 182,780 is one of a new class of steroidal antiestrogens that differs from nonsteroidal antiestrogens, such as tamoxifen, in a number of respects. 1) It is bound by estrogen receptors with a high affinity, similar to that for estradiol. 2) It is a "pure" antiestrogen in that it does not mimic any of the effects of estradiol. 3) This class of antiestrogens does not seem to be bound by antiestrogen binding sites. 4) ICI 182,780 may not be active in the brain after peripheral administration. Indeed, ICI 182,780 blocked in vivo cell nuclear binding of [3H]estradiol in uterus, pituitary, and adipose tissue but not in hypothalamus-preoptic area. In vitro, ICI 182,780 competed for binding by neural estrogen receptors with an affinity comparable with that for estradiol. When given to ovariectomized rats, ICI 182,780 did not mimic any of the actions of estradiol. Instead, ICI 182,780 treatment completely blocked the uterotrophic effects of estradiol and attenuated the actions of estradiol on linear growth, carcass fat content, fat pad weight, and sexual receptivity. Treatment with ICI 182,780 also attenuated the estrogenic effects of tamoxifen on food intake, body weight and composition, linear growth, and uterine weight. These findings support the concept that, in addition to its actions in the brain, estradiol can act peripherally to modulate regulatory behaviors, energy balance, and estrous behavior. They are also consistent with the hypothesis that nonsteroidal antiestrogens, such as tamoxifen, affect energy balance via estrogen receptors, rather than antiestrogen binding sites.
Integrating behavior and cardiovascular responses: posture and locomotion. I. Static analysis
Authors: Smith O. A. , Astley C. A. , Spelman F. A. , Golanov E. V. , Chalyan V. G. , Bowden D. M. , Taylor D. J.
Published: December 2017

Heart rate, arterial blood pressure, and renal and mesenteric or femoral blood flow were telemetered from 11 Papio hamadryas in an untethered free-ranging situation. The animals' behavior was recorded on videotape, and the cardiovascular (CV) data were recorded on the audio channels of the tape. The behavior was coded, and the codes were linked to the CV data via a time-code generator and computer control. The CV data were digitized into 1-s intervals, and the static relations between CV measures and the postures/locomotions (P/Ls) associated with the behavior were analyzed. The total frequency distributions for heart rate, blood pressure, and renal conductance approximated Gaussian distributions, whereas femoral conductance was positively skewed. The distribution for renal conductance suggested that during normal waking conditions the kidney is not maximally dilated and may increase or decrease its blood flow. All distributions were highly influenced by the Sit category, which occupied 80% of the total time. The CV measures for all P/Ls had wide ranges, and the CV values associated with each P/L overlapped those for the other P/Ls. The heart rate and renal conductance associated with the various P/Ls showed the largest deviations from the grand means and therefore contributed the most to the ability to discriminate one P/L from another. Blood pressure varied little from one P/L to another. The patterns of CV variables served to distinguish particular P/Ls very effectively. The frequency distributions were separated best when they were parceled on the basis of the intensity of behavior associated with a particular P/L. These variations in intensity were the major cause of the overlaps in the frequency distributions associated with P/Ls.
Role of prostaglandins on the renal effects of angiotensin and interstitial pressure during volume expansion
Authors: Pinilla J. M. , Alberola A. , Gonzalez J. D. , Quesada T. , Salazar F. J.
Published: December 2017

This study was undertaken to determine, in anesthetized dogs, the role of renal prostaglandins (PG) in mediating the natriuretic response to increased renal interstitial hydrostatic pressure (RIHP) during extracellular volume expansion (ECVE) with isotonic saline. It was also determined if the intrarenal angiotensin II (ANG II) effects during ECVE are potentiated by the inhibition of PG synthesis. ECVE induced similar elevations of RIHP, natriuresis, and fractional lithium excretion in dogs treated (n = 7) and not treated with a PG synthesis inhibitor (n = 5). In other experimental groups, the effects of the intrarenal maintenance of ANG II levels (n = 6) by infusing captopril and ANG II into the right renal artery were compared with those induced by the simultaneous infusion of captopril, ANG II, and a PG synthesis inhibitor (n = 6). In response to ECVE, renal blood flow and glomerular filtration rate were similar in both kidneys when ANG II levels were maintained constant and were significantly higher in the left kidney when ANG II levels were maintained constant and PG synthesis was inhibited in the right kidney. However, when compared with the left kidney, the ECVE-induced increments of natriuresis and RIHP in the right kidney were reduced by the same magnitude when intrarenal ANG II was maintained constant with (36 and 53%, respectively) and without (40 and 54%, respectively) the simultaneous PG synthesis inhibition. Our results indicate that during ECVE, renal PGs do not play an important role in mediating the RIHP-induced increments in natriuresis and decrements in proximal sodium reabsorption. (ABSTRACT TRUNCATED AT 250 WORDS)
Factors associated with vasopressin release in exercising swine
Authors: Stebbins C. L. , Symons J. D. , McKirnan M. D. , Hwang F. F.
Published: December 2017

This study examined the effect of dynamic exercise on vasopressin release in the miniswine and factors that may elicit this response (n = 15). Thus lysine vasopressin (LVP), the catecholamines epinephrine and norepinephrine (EPI and NE), plasma renin activity (PRA), and plasma volume, Na+, and osmolality were measured before and during treadmill running at work intensities of 60, 80, and 100% of each swine's maximal heart rate reserve (HRR). LVP increased in a progressive manner similar to that of humans, ranging from 5.9 +/- 0.4 pg/ml before exercise to 30.1 +/- 4.5 pg/ml during maximal exercise. EPI, NE, and PRA [an index of angiotensin II (ANG II) activity] demonstrated a pattern of response comparable to LVP. Although these hormones can influence the release of LVP, only PRA displayed a strong correlation with LVP (r = 0.84). When ANG II synthesis was blocked (captopril, 1-3 mg/kg, intra-atrial injection) during exercise (80% HRR), plasma LVP was reduced from 9.9 +/- 0.6 to 7.5 +/- 0.6 pg/ml (P < 0.05). In addition, moderate-to-strong correlations were found between plasma concentrations of LVP and plasma osmolality (r = 0.79) and body temperature (r = 0.78). Plasma LVP also correlated with decreases in plasma volume (r = 0.84). These data suggest that the miniswine model is a good one for studying vasopressin effects during exercise and that ANG II appears to be a particularly strong stimulus for the release of this hormone.
Spontaneous waves of cerebral blood flow associated with a pattern of electrocortical activity
Authors: Golanov E. V. , Yamamoto S. , Reis D. J.
Published: December 2017

We examined the relationship between spontaneous changes in regional cerebral blood flow and electrocortical (ECoG) activity in spinalized rats anesthetized with 1.5% isoflurane. Regional cerebral blood flow, measured by laser-Doppler flowmetry, and ECoG activity were measured bilaterally in frontal and parietal cortex. Spontaneous cerebrovascular waves (SCWs) were seen in all (n = 80) rats and consisted of sawtoothed waves with an average amplitude of 20.1 +/- 0.78%, a duration of 11.7 +/- 0.6 s, and a frequency of 6.3 +/- 0.2 min-1. SCWs were always preceded by a high-amplitude burst of ECoG activity (averaging 752.0 +/- 41.8 microV at 5.6 +/- 0.2 Hz) and comparable to the well-recognized burst-suppression/barbiturate-spindle patterns of ECoG activity. The latency between bursts and SCWs averaged 1.71 +/- 0.05 s. The frequency of bursts and SCWs was highly correlated within and between cortical areas bilaterally (r > 0.9) and appeared synchronously across brain. Deepening anesthesia (to 1.75% isoflurane) reduced the frequency of bursts and SCWs by > 30% but not their correlation (r > 0.9) and minimally increased burst-SCW latency. SCWs differed from an uncommon sinusoidal oscillation regional cerebral blood flow triggered by changes in arterial pressure and independent of the ECoG. Bursts and SCWs were not affected by inhibition of nitric oxide synthase. The results indicate that a population of local cortical neurons, probably driven from subcortical pacemakers, when excited, elicits local cerebrovascular vasodilation.
Role of vasopressin in sympathetic response to paraventricular nucleus stimulation in anesthetized rats
Authors: Malpas S. C. , Coote J. H.
Published: December 2017

Vasopressin may play an extrahypothalamic role in the central control of the cardiovascular system, specifically acting as a spinal neurotransmitter in the pathway where the paraventricular nucleus (PVN) alters sympathetic outflow. In this study, the effect of stimulating neuronal cell bodies in the PVN on renal sympathetic nerve activity (RSNA) and the possible involvement of vasopressin in the pathway was investigated in anesthetized rats. The PVN was stimulated by microinjection with 0.2 M D,L-homocysteic acid via a glass micropipette, and the hemodynamic and sympathetic responses were recorded. A computerized sympathetic peak-detection algorithm was applied to recordings of sympathetic discharges to retrieve information about the characteristics of RSNA during PVN stimulation. The algorithm scanned the series of RSNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RSNA peak had been detected, its corresponding amplitude and peak-to-peak interval were calculated. PVN stimulation consistently increased the amplitude of RSNA (mean 30 +/- 5.6% over control), arterial pressure, and the peak-to-peak interval of discharges. A V1 vasopressin antagonist intrathecally administered as a 500-pmol dose was subsequently able to completely block the hemodynamic response (blood pressure increase of 14 +/- 5%) and a 35 +/- 6% increase in RSNA in response to PVN stimulation and intrathecal vasopressin. Thus spinal vasopressin is likely to be a neurotransmitter involved in the cardiovascular regulation involving the PVN.
Mechanisms for the tachypneic response to the thromboxane A2 mimetic U-46,619 in rabbits
Authors: Carrithers J. A. , Liu F. , Shirer H. W. , Orr J. A.
Published: December 2017

These experiments were designed to determine if intravenous infusion of the thromboxane A2 mimetic, U-46,619, would elicit tachypnea in the rabbit, and if so whether the afferent signal was generated by receptors innervated by myelinated or unmyelinated vagal nerve fibers. Intravenous infusion of U-46,619 (0.5 microgram/kg delivered over 10 s) increased breathing frequency (26%) and right ventricular blood pressure (59%) in the anesthetized rabbit (n = 10). Systemic arterial blood pressure, heart rate, and tidal volume were unaffected by the infusion of U-46,619. When myelinated fiber conduction in the vagus nerve was eliminated by bilaterally cooling the nerve to 6 degrees C, the increase in breathing frequency was only 5% above baseline levels. The tachypneic response to U-46,619 was totally eliminated when both myelinated and unmyelinated fiber conduction was abolished by cooling the vagi to 0 degree C. The increase in right ventricular blood pressure after U-46,619 infusion was unaffected by vagal cooling. Because most (> 80%) of the tachypneic response to U-46,619 was eliminated by blockade of myelinated vagal fiber conduction, we conclude that the tachypneic response to U-46,619 is mediated mostly by receptors innervated by myelinated vagal afferent fibers in the anesthetized rabbit.
PNMT-containing neurons of the C1 cell group express c-fos in response to changes in baroreceptor input
Authors: Sved A. F. , Mancini D. L. , Graham J. C. , Schreihofer A. M. , Hoffman G. E.
Published: December 2017

The immunocytochemical detection of Fos, the protein product of the immediate-early gene c-fos, was used as a marker for activated neurons to examine whether the C1 neurons in the rat rostral ventrolateral medulla (RVLM) respond to changes in baroreceptor afferent activity. After hydralazine-induced hypotension or sinoaortic denervation, two treatments that reduce baroreceptor afferent activity, numerous Fos-positive neurons were observed in the RVLM. The number of Fos-positive neurons in the RVLM was counted in brain stem sections from hydralazine-treated rats that had been previously injected with Fluorogold into the upper thoracic spinal cord to label spinally projecting RVLM neurons as well as stained for phenylethanolamine-N-methyltransferase (PNMT) as a marker of C1 neurons. The results indicate that approximately 80% of the C1 neurons expressed Fos in response to hydralazine injection; this was true of spinally projecting C1 neurons as well as those C1 neurons that were not labeled with Fluorogold. Furthermore, in hydralazine-treated rats, the majority of Fluorogold-labeled Fos-positive neurons contained PNMT. These results suggest that C1 neurons are sensitive to baroreceptor afferent input and support a role of these neurons in cardiovascular regulation.
Metabolic response to ambient temperature and hypoxia in sinoaortic-denervated rats
Authors: Matsuoka T. , Dotta A. , Mortola J. P.
Published: December 2017

We tested the hypothesis that the sinoaortic afferents may contribute to normoxic thermogenesis and to the magnitude of the hypometabolic response to hypoxia. Adult rats were either sinoaortic denervated (SAX; n = 20) or sham operated (Sham; n = 20). A few days after the operation, gaseous metabolism [O2 uptake (VO2) and CO2 production (VCO2)] was measured with an open-flow system at ambient temperatures (Tamb) of 20, 25, 30, and 35 degrees C as the animal was resting awake. At thermoneutrality (Tamb 30 degrees C) or higher Tamb there was no difference in VO2 or VCO2. Below thermoneutrality, metabolic rate was significantly lower in SAX than in Sham animals (-14 and -16% at 20 and 25 degrees C, respectively). Colonic temperature and arterial PO2 were also slightly less, whereas arterial PCO2 and pH, mean arterial pressure, and heart rate did not differ significantly between the two groups. Exposure to acute hypoxia (10% inspired O2, 20-30 min) at Tamb 20 and 25 degrees C significantly reduced VO2 in both groups to a similar value; hence, at either Tamb, the metabolic drop during hypoxia in Sham animals was larger than that in SAX animals. Hypercapnia (5% CO2 breathing) did not change VO2 in either group. We conclude that in the rat at Tamb slightly below thermoneutrality, the sinoaortic afferents 1) provide a small but significant contribution to normoxic thermogenesis and 2) are not required for the manifestation of the drop in metabolism during hypoxia.
Whole body and splanchnic leucine, phenylalanine, and glucose kinetics during endotoxemia in humans
Authors: Fong Y. , Matthews D. E. , He W. , Marano M. A. , Moldawer L. L. , Lowry S. F.
Published: December 2017

To examine the whole body and splanchnic tissue substrate handling during endotoxemia, an intravenous bolus of endotoxin was given to six healthy volunteers during primed, continuous infusions of [1-13C]leucine, [ring-2H5]phenylalanine, and [6,6-2H2]glucose. Whole body protein breakdown, based on whole body Leu and Phe appearance rates (Ra), increased in response to endotoxin given at time 0 (RaLeu 77 +/- 2 mol.kg-1 x h-1, t = 0 h; 88 +/- 6, t = 4 h; P < 0.05) (RaPhe 39 +/- 2 mol.kg-1 x h-1, t = 0; 46 +/- 3, t = 4 h; P < 0.05). Splanchnic amino acid balance (Bal) increased (BalLeu 7 +/- 4 mol.kg-1 x h-1, t = 0; 21 +/- 5, t = 2 h; P < 0.05) (BalPhe 3 +/- 2 mol.kg-1 x h-1, t = 0; 16 +/- 4, t = 2 h; P < 0.05) and can be accounted for by increased splanchnic uptake (Rd) of Phe and Leu (RdLeu 21 +/- 3 mol.kg-1 x h -1, t = 0; 37 +/- 7, t = 120 min; P < 0.05) (RdPhe 10 +/- 3 mol.kg-1 x h-1, t = 0; 24 +/- 5, t = 120 min; P < 0.05). Splanchnic conversion of Leu to ketoisocaproate increased with endotoxin administration (0.7 +/- 0.6 mol.kg-1 x h-1, t = 0; 8 +/- 3, t = 360 min; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Monoamine concentrations in cerebrospinal fluid of fetal and newborn sheep
Authors: Joseph S. A. , Walker D. W.
Published: December 2017

Monoamine concentrations were measured in cisternal cerebrospinal fluid (CSF) of unanesthetized fetal (115-135 days gestation) and newborn (2-34 days old) sheep. Norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations decreased with gestational age; NE CSF concentrations were significantly higher in the newborn (336.4 +/- 61.7 pg/ml; n = 5) compared with the 131- to 135-day-gestation fetuses (104.0 +/- 46.3 pg/ml, n = 3; P < 0.05). Dopamine (DO), homovanillic acid (HVA), and serotonin (5-HT) concentrations in fetal CSF did not change with gestational age, and epinephrine (Epi) was undetectable in most fetal and newborn samples. Hypoxia, induced by giving the ewe 9% O2 in N2 to breathe for 30 min, resulted in a 10.78 +/- 3.94-fold (n = 5) increase of NE concentration in fetal CSF (P < 0.05); DO and DOPAC concentrations did not change. Hypoxia did not increase NE concentrations in CSF of newborn lambs. Inhibition of prostaglandin (PG) synthesis by intravenous infusion of indomethacin significantly reduced plasma prostaglandin E2 concentrations from 7.8 +/- 1.0 (n = 6) to 2.5 +/- 0.2 nmol/l (n = 3; P < 0.05), and was associated with an increase of CSF DOPAC concentrations from 2,156.3 +/- 504.5 (n = 9) to 5,453.6 +/- 1,091.3 pg/ml (n = 5; P < 0.05); NE and DO concentrations did not change significantly. These results show that catecholamines and indoleamines are released in the brain and enter the CSF of fetal sheep from at least 115 days gestation. The data also show that concentrations of some monoamines in CSF are changed by fetal hypoxia or prostaglandin synthesis.
Insulin acts centrally to enhance reflex tachycardia in conscious rats
Authors: Okada M. , Bunag R. D.
Published: December 2017

Systemic and central insulin treatment for 10 days were compared in conscious rats given insulin either by daily subcutaneous injection or by continuous intracerebroventricular infusion. To measure changes in baroreflex sensitivity, heart rate responses elicited reflexly by elevating blood pressure with phenylephrine or lowering it with sodium nitroprusside were recorded before and after insulin treatment. Although reflex bradycardia and basal mean pressures and heart rates were unaffected, reflex tachycardia was consistently more pronounced in rats treated with insulin (whether given systemically or centrally) than in vehicle-treated controls. Plasma glucose was reduced and plasma insulin was elevated but only in insulin-treated rats injected subcutaneously and not in those infused intracerebroventricularly. Inasmuch as reflex tachycardia was still enhanced when insulin was infused intracerebroventricularly despite the absence of hypoglycemia and hyperinsulinemia, our results are compatible with the interpretation that insulin acts directly on the brain to enhance reflex tachycardia. This interpretation furthermore implies that insulin, even after chronic systemic treatment, could reach the brain and alter baroreflex regulation.
Pressure-dependent renin release and arterial pressure maintenance in conscious rats
Authors: Bertolino S. , Julien C. , Medeiros I. A. , Vincent M. , Barres C.
Published: December 2017

The relationship between pressure-dependent renin release and mean arterial pressure (MAP) level was assessed in normotensive intact (n = 10), sympathectomized (guanethidine at 1-13 wk of age; n = 8), and renal-denervated (1 wk before the study; n = 6) rats under normal-salt diet. MAP was recorded beat-to-beat for 2 h in conscious animals. Then plasma renin concentration (PRC) responses to graded reductions of MAP were determined using an aortic inflatable cuff. Neither sympathectomy nor renal denervation altered baseline MAP level and PRC. Lowering MAP below a threshold pressure induced large increases in PRC. Threshold pressure did not differ between intact (87 +/- 1 mmHg), sympathectomized (88 +/- 2 mmHg), and renal-denervated (83 +/- 2 mmHg) rats. MAP frequently fell below threshold pressure in sympathectomized but not in intact and renal-denervated rats. We conclude that in conscious normotensive quiet rats under normal-salt diet the pressure-dependent renin release is not activated spontaneously and is therefore unlikely to play a role in MAP maintenance. This regulatory mechanism develops and operates normally in the absence of sympathetic nerves.
Effects of growth hormone on gill chloride cells in juvenile Atlantic salmon (Salmo salar)
Authors: Prunet P. , Pisam M. , Claireaux J. P. , Boeuf G. , Rambourg A.
Published: December 2017

Experiments were performed to investigate the effects of ovine growth hormone (oGH) on both the ultrastructural features of chloride cells and the ability of gills to extrude Na+ after transfer into seawater. February presmolts and June parrs of the Atlantic salmon (Salmo salar) were implanted with oGH. In such animals, spontaneously showing a poor ability to adapt themselves to seawater life, GH significantly increased gill Na(+)-K(+)-adenosinetriphosphatase activity as well as gill sodium efflux into seawater. When examined by electron microscope, two types of chloride cells (alpha- and beta-types) were identified in control parrs and presmolts. GH treatment induced an increase in size and number of alpha-cells that displayed an extensive tubular system, while the beta-cells, thought to be specific to freshwater life, decreased in number. There was, concomitantly, an increase in number of accessory cells associated with the apical portion of the alpha-cells and, as a result, the formation of extensive shallow junctions between these cell types. Such functional and ultrastructural modifications that mimicked those naturally occurring during the last steps of the smoltification strongly suggest that GH stimulates the differentiation of freshwater chloride cells toward a seawater type.