bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of AMPA/kainate receptors in transmission of the sympathetic baroreflex in rat CVLM
Authors: Miyawaki T. , Suzuki S. , Minson J. , Arnolda L. , Chalmers J. , Llewellyn-Smith I. , Pilowsky P.
Published: December 2017

We examined the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors within the caudal ventrolateral medulla (CVLM) in mediating the sympathetic baroreceptor reflex in anesthetized and paralyzed rats. Bilateral microinjection into CVLM of either DL-2-amino-5-phosphonovaleric acid [APV; a selective N-methyl-D-aspartic acid (NMDA) receptor antagonist, 20 mM, 100 nl] or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; a selective AMPA/kainate receptor antagonist, 2 mM, 100 nl) alone failed to eliminate the aortic nerve stimulation-evoked hypotension and inhibition of splanchnic sympathetic nerve activity (SNA) or the cardiac-related rhythmicity of SNA. All components of the sympathetic-baroreceptor reflex were abolished when kynurenate (100 mM, 30 nl) or mixtures of APV and CNQX (10 and 1 mM, respectively, 100 or 30 nl) were injected into CVLM. Injection of APV or CNQX into CVLM reduced aortic nerve-evoked inhibitory responses of bulbospinal sympathoexcitatory neurons in rostral ventrolateral medulla (RVLM). The extent of this reduction was variable. Usually, significant inhibition was preserved. In seven RVLM neurons, intravenous injection of MK-801 (NMDA receptor antagonist, 2 mg/kg) failed to eliminate aortic nerve-evoked inhibitory responses. However, inhibitory responses were abolished when CNQX was injected into CVLM after intravenous MK-801. We conclude that both NMDA and AMPA/kainate receptors in CVLM transmit baroreceptor information.
Proadrenomedullin NH2-terminal 20 peptide has direct vasodilator activity in the cat
Authors: Champion H. C. , Murphy W. A. , Coy D. H. , Kadowitz P. J.
Published: December 2017

The mechanism by which proadrenomedullin NH2-terminal 20 peptide (PAMP) decreases vascular resistance was investigated in the hindlimb vascular bed in the cat. Injections of PAMP, a shortened form of the peptide PAMP-(12-20), and adrenomedullin (ADM) into the hindlimb perfusion circuit elicit dose-related decreases in perfusion pressure. The order of potency was ADM > PAMP > PAMP-(12-20), and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) had no effect on vasodilator responses to PAMP or ADM. Vasodilator responses to PAMP were increased in duration by the adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor Rolipram, whereas inhibitors of nitric oxide synthase and guanosine 3',5'-cyclic monophosphate phosphodiesterase had no effect. Vasodilator responses to PAMP were not altered by treatment with alpha-receptor or adrenergic nerve terminal blocking agents and were similar in innervated and denervated hindlimb preparations. Responses to PAMP were similar when vasoconstrictor tone was increased by stimulation of the sympathetic nerves or infusion of phenylephrine and were not altered by the passage of time. These data suggest that PAMP dilates the hindlimb vascular bed by a direct cAMP-dependent mechanism and that inhibition of norepinephrine release plays little if any role in mediating responses to the peptide in the regional vascular bed of the cat.
Sympathetic activation cannot fully account for increased plasma renin levels during water deprivation
Authors: Blair M. L. , Woolf P. D. , Felten S. Y.
Published: December 2017

This study was designed to determine if the increase in plasma renin activity (PRA) that occurs during water deprivation is mediated by the renal sympathetic nerves or adrenomedullary catecholamine release. Male Sprague-Dawley rats were studied while conscious and unrestrained. In intact or sham-operated rats, 48 h of water deprivation resulted in at least a threefold increase in PRA and plasma renin concentration (PRC) but no significant change in plasma norepinephrine or epinephrine concentration. Renal denervation decreased basal PRA, reduced the magnitude of the dehydration-induced PRA increase by 33%, and abolished the renin-suppressing effect of l-propranolol infusion in water-deprived rats. Adrenal demedullation also reduced basal and water-deprived PRA and PRC. However, even the combination of renal denervation and adrenal demedullation did not prevent a significant renin response to dehydration (control PRA of 1.8 +/- 0.6 ng x ml(-1) x h(-1) to dehydration PRA of 6.8 +/- 1.3 ng x ml(-1) x h(-1), P < 0.05). Therefore, some mechanism in addition to sympathoadrenomedullary activation plays a major role in mediating increased PRA during water deprivation.
Individual differences in response to LPS and psychological stress in aged rats
Authors: Wachulec M. , Peloso E. , Satinoff E.
Published: December 2017

Old rats may show blunted fever or hypothermia after injection of lipopolysaccharide (LPS), a fever-producing agent, and have a reduced body temperature (Tb) rise in response to psychological stress. These results may partly be a consequence of aging per se, partly a sex difference, and partly an effect of differences in types and doses of pyrogen. Here we tested age and gender differences in Tb responses to 30-min exposure to a novel environment and to injection of several doses of LPS. There were age-related reductions in novelty-induced hyperthermia, and some old rats even became hypothermic. Sensitivity to the pyrogenic activity of LPS and to the toxic effects of endotoxin (manifested by hypothermia) both increased in aged female rats. A major finding was that there were no correlations between age-related changes in Tb in response to novelty and to LPS injection. Tb responses in aged rats were variable; in each situation, there were old rats whose Tb rose as high as did younger ones. We did not observe significant gender differences in response either to novelty or to LPS in young or old rats.
Effects of A-23187 and verapamil on the active transport enzymes in turtle bladder epithelial cells
Authors: Sabatini S.
Published: December 2017

These experiments were designed to examine the effects of A-23187 (5 x 10(-4) M) and verapamil (100 microM) on membrane transport, 45Ca fluxes, and adenosine-triphosphatase (ATPase) activities in turtle bladder. In the intact membrane, the calcium ionophore decreased proton secretion and sodium transport [short-circuit current (SCC)] to approximately the same degree (by approximately 55% at 30 min). During the same period of time, verapamil decreased SCC (by approximately 58%), but proton secretion was unaffected. The turtle bladder membrane is composed predominantly of two cell types: 1) the mitochondrial-rich cells (MR cells) thought to be involved in proton (and bicarbonate) secretion containing significant H(+)-ATPase and Ca(2+)-ATPase and 2) the granular cells (G cells), postulated important in sodium reabsorption, having abundant Na(+)-K(+)-ATPase. That Na(+)-K(+)-ATPase activity was unchanged by either a calcium ionophore or a calcium channel blocker suggests that the decrease in SCC noted in the intact membrane is not directly mediated by changes in the sodium "pump." The decrease of H(+)-ATPase in MR cells, which resulted after the A-23187, suggests that it probably exerts a direct action on the proton pump, which decreases hydrogen ion secretion. The increase in ATP-dependent 45Ca transport seen after the ionophore (or the decrease in ATP-independent 45Ca transport after verapamil) most likely reflects increased (or decreased) Ca2+ availability within the cytosol, and the high (or low) cell calcium could decrease the SCC. These results thus suggest that cytosolic Ca2+ reciprocally sets, by different mechanisms, the rate of proton secretion in MR cells and the sodium reabsorption in G cells.
Effects of inhalation anesthetics on parasympathetic reflex vasodilation in the lower lip and palate of the cat
Authors: Izumi H. , Ito Y. , Sato M. , Karita K. , Iwatsuki N.
Published: December 2017

The present experiments were designed to examine the effects of inhalation anesthetics (isoflurane, halothane, and sevoflurane) on the parasympathetic reflex vasodilation in the lower lip and palate elicited by electrical stimulation of the central cut end of the lingual nerve in vagosympathectomized cats. Isoflurane (1.5%), halothane (1.0%), and sevoflurane (2.5%), each at a concentration of 1.0 minimum alveolar concentration, markedly suppressed the evoked blood flow increases in the lower lip, whereas nitrous oxide (70% in 30% oxygen) and morphine (2 mg/kg iv) did not. Prior administration of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist (2 mg/kg iv), reversed the inhibitory effect of isoflurane on the parasympathetic reflex response. Decerebration had no significant effect on the isoflurane-induced inhibition. These findings suggest that there is a GABA-mediated suppressive mechanism acting on this parasympathetic reflex response; the sites at which inhalation anesthetics exert such an inhibitory action could be in the midbrain, pons, or medulla, but not in the hypothalamus or higher structure.
Effect of autonomic blockade on power spectrum of heart rate variability during exercise
Authors: Warren J. H. , Jaffe R. S. , Wraa C. E. , Stebbins C. L.
Published: December 2017

To validate power spectral analysis of heart rate variability (HRV) as an autonomic indicator during exercise, ten males performed four identical progressive cycling tests during infusions of saline, esmolol (beta 1-blocker), glycopyrrolate (muscarinic blocker), or both drugs. Power spectra were constructed from the recorded electrocardiogram by Fourier algorithm and integrated for low-frequency power (LF) and high-frequency power (HF). Four different LF bands (0.004-0.1, 0.004-0.15, 0.05-0.1, and 0.05-0.15 Hz) and two different HF bands (0.1-1.0 and 0.15-1.0 Hz) were evaluated. The parasympathetic index, HF, decreased exponentially with workload and was attenuated by glycopyrrolate and combined treatments with both HF frequency bands measured. Whereas some sympathetic indexes (LF/total power and LF/HF) did reflect expected increases in sympathetic nerve activity associated with progressive increases in work intensity, none of the measured increases responded appropriately to autonomic blockade. It is concluded that HRV is a valid technique for noninvasive measurement of parasympathetic tone during exercise, but its validity as a measure of sympathetic tone during exercise is equivocal.
Age-related changes in the pressure diuresis and natriuresis response
Authors: Vargas F. , Ortiz M. C. , Fortepiani L. A. , Atucha N. M. , Garcia-Estan J.
Published: December 2017

The renal-excretory responses to changes in renal perfusion pressure (RPP) were studied in anesthetized young (3 mo old), adult (12 mo old), and senescent (24 mo old) rats to evaluate whether the pressure diuresis and natriuresis mechanism is altered as a function of age. Experiments were performed in anesthetized animals in which nervous and systemic hormonal influences to the kidney were fixed. Mean arterial pressure was similar in all three groups: 97.6 +/- 2.6, 102.1 +/- 3.7, and 95.2 +/- 5.2 mmHg in young, adult, and senescent rats, respectively. The relationships between RPP and diuresis/natriuresis or fractional excretions of water and sodium were similar in young and adult rats. However, in senescent rats the pressure-diuretic and pressure-natriuretic responses were slightly shifted to the right, so that diuresis and natriuresis were significantly lower at higher levels of RPP. Glomerular filtration rate was well autoregulated, and there were no differences between young and adult rats at each level of RPP. However, a significantly lower glomerular filtration rate was observed in senescent rats. These results indicate an age-related decline in the pressure-dependent sodium and water excretion that appears to be due to a decrease in glomerular filtration and an increase in tubular sodium reabsorption.
Expression and secretion of lipocortin 1 in gut inflammation are not regulated by pituitary-adrenal axis
Authors: Vergnolle N. , Comera C. , More J. , Alvinerie M. , Bueno L.
Published: December 2017

Lipocortin 1 is considered a mediator of the anti-inflammatory actions of glucocorticoids. We have shown that this protein is overexpressed and secreted during an experimental colitis induced by intraluminal injection of trinitrobenzenesulfonic acid (TNBS) in rats. We studied here the in vivo regulation of lipocortin 1 expression and secretion in this model, either by glucocorticoids using adrenalectomized or dexamethasone-treated (3 mg/24 h) animals or by pituitary factors using hypophysectomized animals. Inflammation was evaluated by measuring myeloperoxidase activity and by histological scoring of the damage. Lipocortin 1 was detected by immunoblotting, and its secretion was studied by incubating colonic specimens in-culture medium. In the colon of TNBS-injected animals, cumulative histological damage scores were increased in adrenalectomized and decreased in dexamethasone-treated animals compared with control and hypophysectomized animals. The colons of all TNBS-injected animals (controls, adrenalectomized, dexamethasone treated, hypophysectomized) overexpressed and secreted lipocortin 1. In conclusion, the induction of lipocortin 1 overexpression and secretion during this colitis occurs independently of glucocorticoids or pituitary factors.
Short-day weight loss and effect of food deprivation on hypothalamic NPY and CRF mRNA in Djungarian hamsters
Authors: Mercer J. G. , Lawrence C. B. , Moar K. M. , Atkinson T. , Barrett P.
Published: December 2017

The effect of food deprivation on hypothalamic neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) gene expression in the Djungarian hamster was quantified by in situ hybridization. Hamsters housed in short days (SD) for 18 wk decreased body weight by 40% and exhibited 200% increases in both NPY and CRF mRNA when deprived of food for 24 h. Prior gonadectomy in long days (LD) affected neither basal gene expression nor the induction of gene expression by food deprivation. Gene expression in juvenile LD hamsters similar in body weight to SD animals was relatively insensitive to food deprivation of either 24- or 48-h duration or to subsequent refeeding. In juvenile hamsters, food deprivation for 24 but not 48 h decreased ob (obese) gene expression in inguinal but not epididymal white adipose tissue; ob mRNA levels were restored by refeeding. All food-deprived hamsters had reduced plasma insulin concentrations, but plasma cortisol was only elevated in SD food-deprived animals. NPY gene expression was also increased after daily dexamethasone injections in adult LD hamsters. These results suggest that the neuroendocrine consequences of food deprivation in SD Djungarian hamsters are determined by some factor other than absolute body mass such as the size of adipose tissue reserves.
Skin sympathetic outflow during head-down neck flexion in humans
Authors: Ray C. A. , Hume K. M. , Shortt T. L.
Published: December 2017

We have previously demonstrated increases in muscle sympathetic nerve activity during head-down neck flexion (HDNF). The purpose of the present study was to determine if HDNF also activates skin sympathetic nerve activity (SSNA). SSNA, heart rate, arterial pressure, skin blood flow, calf blood flow, and calculated calf vascular resistance (mean arterial pressure/calf blood flow) were determined in 12 subjects during 3 min of baseline (lying prone with chin supported) and 3 min of HDNF. There were no significant changes in heart rate and arterial pressures during HDNF; however, diastolic and mean arterial pressure tended to increase slightly. Calf blood flow decreased 22% and calf vascular resistance increased 46% during HDNF. SSNA did not significantly change during HDNF. In three subjects we measured both muscle and skin sympathetic nerve activity during HDNF. In these trials, muscle sympathetic nerve activity consistently increased, but SSNA did not. The results indicate that HDNF in humans activates muscle sympathetic nerve activity, but does not activate SSNA. Thus vestibular stimulation may elicit differential activation of sympathetic outflow in humans.
ANG II prolongs splanchnic nerve-mediated inhibition of duodenal mucosal alkaline secretion in the rat
Authors: Johansson B. , Holm M. , Chen L. , Pettersson A. , Jonson C. , Fandriks L.
Published: December 2017

Hypovolemia inhibits duodenal mucosal alkaline (HCO-3) secretion by activation of sympathoadrenergic nerves. A possible involvement of the renin-angiotensin system was investigated. Experiments were performed on chloralose-anesthetized rats. The mucosal alkaline output by a duodenal segment was measured using in situ pH-stat titration equipment. A modest hypovolemia was induced by bleeding the animals approximately 10% of the total blood volume. This procedure decreased duodenal mucosal alkaline secretion to a sustained level of approximately 50% of baseline and reduced mean arterial pressure by approximately 20 mmHg. Intravenous pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalaprilate (0.7 mg/kg) or the angiotensin II-receptor antagonist losartan (10 mg/kg) altered the response to hypovolemia to a transient one, and alkaline secretion returned to the control level within 40-50 min. When exogenous angiotensin II was administered intravenously (0.25 and 0.75 microgram.kg-1.h-1), a hypovolemia-induced sustained depression of the secretion was observed even during ACE inhibition. Direct electrical stimulation (3 Hz, 5 V, 5 ms, bilaterally) of the peripheral splanchnic nerves decreased duodenal mucosal alkaline secretion to approximately 60% of the control level and increased mean arterial pressure by approximately 20 mmHg. However, in enalaprilate-pretreated animals, the inhibition of alkaline secretion due to splanchnic nerve stimulation was transient, a response that became sustained on angiotensin II substitution. These results suggest that the renin-angiotensin system prolongs the sympathoadrenergic inhibition of duodenal mucosal alkaline secretion and that angiotensin II, in this regard, acts mainly on the peripheral sympathetic efferents.
Targets for SMR1-pentapeptide suggest a link between the circulating peptide and mineral transport
Authors: Rougeot C. , Vienet R. , Cardona A. , Le Doledec L. , Grognet J. M. , Rougeon F.
Published: December 2017

The submandibular rat 1 protein (SMR1) is selectively processed at pairs of basic amino acid residues in a tissue- and sex-specific manner. We have mapped peripheral targets for the final secretory maturation product of SMR1, the pentapeptide QHNPR, by examining in vivo the tissue distribution of the radiolabeled peptide using β-radio imager whole body autoradiography. The characteristics of tissue uptake allowed specific binding sites at physiological peptide concentrations to be identified within the renal outer medulla, bone and dental tissue, glandular gastric mucosa, and pancreatic lobules. Direct evidence that pentapeptide binding sites are localized in selective portions of the male rat nephron, within the S3, S2, and S1 segments of the proximal tubules, was obtained. In bone tissue the pentapeptide exclusively accumulates within the trabecular bone remodeling unit, and in dental tissue it concentrates within the tubules of the dentinal rat incisor. In relation to male rat-specific behavioral characteristics, our data suggest that the circulating androgen-regulated SMR1-derived pentapeptide is primarily involved in the modulation of mineral balance between at least four systems: kidney, bone, tooth, and circulation.
Adrenal epinephrine and norepinephrine release to hypoglycemia measured by microdialysis in conscious rats
Authors: Vollmer Regis R. , Balcita Judith Joyce , Sved Alan F. , Edwards David J.
Published: December 2017

Experiments were conducted in conscious male rats to determine whether hypoglycemia induced by insulin administration preferentially stimulated epinephrine (Epi) or norepinephrine (NE) adrenal medullary chromaffin cells. The release of Epi and NE from the adrenal medulla was continuously monitored using a microdialysis probe of novel design that had been inserted in the adrenal medulla ∼16 h before the administration of insulin. Following insulin, 3 U/kg iv, blood glucose declined and dialysate Epi levels rose. No measurable increment in dialysate NE was obtained. Similarly, plasma Epi increased with no detectable change in NE. Patterns of dialysate and plasma catecholamine changes were similar in two groups of animals that had been fed or fasted overnight before insulin treatment. However, the magnitude of the Epi increase was greater in the fasted animals. After recovery of the blood glucose concentration to preinsulin levels, dialysate and plasma catecholamine concentrations returned to control values. These experiments clearly demonstrate that adrenal medullary chromaffin cells that produce Epi are preferentially stimulated in response to insulin-induced hypoglycemia.
The thermoregulatory mechanism of melatonin-induced hypothermia in chicken
Authors: Rozenboim I. , Miara L. , Wolfenson D.
Published: December 2017

The involvement of melatonin (Mel) in body temperature (Tb) regulation was studied in White Leghorn layers. In experiment 1, 35 hens were injected intraperitoneally with seven doses of Mel (0, 5, 10, 20, 40, 80, or 160 mg Mel/kg body wt) dissolved in ethanol. Within 1 h, Mel had caused a dose-dependent reduction in Tb. To eliminate a possible vehicle effect, 0, 80, and 160 mg/kg body wt Mel dissolved in N-methyl-2-pyrrolidone (NMP) was injected. NMP had no effect on Tb, with Mel again causing a dose-dependent hypothermia. In experiment 2 ( n= 30), Mel injected before exposure of layers to heat reduced Tb and prevented heat-induced hyperthermia. Injection after heat stress had begun did not prevent hyperthermia. Under cold stress, Mel induced hypothermia, which was not observed in controls. In experiment 3 ( n= 12), Mel injection reduced Tband increased metatarsal and comb temperatures (but not feathered-skin temperature), respiratory rate, and evaporative water loss. Heart rate rose and then declined, and blood pressure increased 1 h after Mel injection. Heat production rose slightly during the first hour, then decreased in parallel to the Tbdecline. We conclude that pharmacological doses of Mel induce hypothermia in hens by increasing nonevaporative skin heat losses and slightly increasing respiratory evaporation.
Effect of the nitric oxide level in the medial preoptic area on male copulatory behavior in rats
Authors: Sato Yoshikazu , Horita Hiroki , Kurohata Toshie , Adachi Hideki , Tsukamoto Taiji
Published: December 2017

We investigated the influence of the extracellular nitric oxide (NO) level on male copulatory behavior. We confirmed the changes of nitrite ([Formula: see text]) and nitrate ([Formula: see text]) in the medial preoptic area (MPOA) by administration of the NO precursorl-arginine (l-Arg, 10 mM) or the NO synthase inhibitor N G-monomethyl-l-arginine (l-NMMA, 10 mM) via a dialysis probe. [Formula: see text] and[Formula: see text] were measured simultaneously by an in vivo microdialysis method coupled with the Griess reaction.l-Arg induced significant elevations of extracellular [Formula: see text]and [Formula: see text].l-NMMA significantly reduced[Formula: see text] and[Formula: see text] levels. We observed male copulatory behavior during infusion ofl-Arg orl-NMMA. The mount rate of male rats significantly increased during infusion ofl-Arg in the MPOA. Administration of l-NMMA reduced the mount rate. These findings suggested that the elevation of extracellular NO in the MPOA facilitates male copulatory behavior of rats, whereas the decrease of NO reduces their copulatory behavior.
Suppression of renal sympathetic nerve activity during portal vein infusion of hypertonic saline
Authors: Nishida Yasuhiro , Sugimoto Isao , Morita Hironobu , Murakami Hiroshi , Hosomi Hiroshi , Bishop Vernon S.
Published: December 2017

Sodium ions absorbed from the intestine are postulated to act on the liver to reflexly suppress renal sympathetic nerve activity (RSNA), resulting in inhibition of sodium reabsorption in the kidney. To test the hypothesis that the renal sympathoinhibitory response to portal venous NaCl infusion involves an action of arginine vasopressin (AVP) at the area postrema, we examined the effects of portal venous infusion of hypertonic NaCl on RSNA before and after lesioning of the area postrema (APL) or after pretreatment with an AVP V1 receptor antagonist (AVPX). Rabbits were chronically instrumented with portal and femoral venous catheters, femoral arterial catheters, and renal nerve electrodes. Portal venous infusion of 9.0% NaCl (0.02, 0.05, 0.10, and 0.15 ml ⋅ kg−1 ⋅ min−1of 9.0% NaCl for 10 min) produced a dose-dependent suppression of RSNA (−12 ± 3, −34 ± 3, −62 ± 5, and 80 ± 2%, respectively) that was greater than that produced by femoral vein infusion of 9.0% NaCl (2 ± 3, −3 ± 2, −12 ± 4, and −33 ± 3%, respectively). The suppression of RSNA produced by portal vein infusion of 9.0% NaCl was partially reversed by pretreatment with AVPX (−9 ± 3, −20 ± 3, −41 ± 4, and −55 ± 4%, respectively) and by APL (−11 ± 2, −25 ± 2, −49 ± 3, and −59 ± 6%, respectively). There were no significant differences between the effects of AVPX and APL, and the effect of APL was not augmented by AVPX. These results indicate that the suppression of RSNA due to portal venous infusion of 9.0% NaCl involves an action of AVP via the area postrema.
Effects of baclofen on the Hering-Breuer inspiratory-inhibitory and deflation reflexes in rats
Authors: Seifert Erin , Trippenbach Teresa
Published: December 2017

The objective of this study was to evaluate effects of baclofen, a γ-aminobutyric acid type B (GABAB) receptor agonist, injected into the nucleus of the solitary tract, on the Hering-Breuer inspiratory-inhibitory (Ti-inhibitory) and deflation reflexes in urethan-anesthetized adult Wistar rats ( n = 7). The Ti-inhibitory reflex was estimated from changes in peak amplitude of the integrated diaphragmatic electromyogram and inspiratory time (Ti) provoked by airway occlusion at end expiration. The deflation reflex was evaluated from changes in Ti and expiration (Te) of the first two breaths (Ti-1, Te-1 and Ti-2, Te-2) immediately after a decrease in tracheal pressure (Ptr). Under control conditions, airway occlusion at end-Te prolonged Ti (66 ± 5%; mean ± SE) and the following Te (54 ± 11%). Decreases in Ptr, from −2 to −5 cmH2O, evoked an increase in Ti and shortening of Te of both breaths. Both effects were Ptr dependent, and Ti-1 and Te-1 differed from Ti-2 and Te-2, suggesting a rapid adaptation to the stimulus. At Ptr of −5 cmH2O, Ti-1 and Ti-2 increased by 30 ± 2 and 43 ± 6%, respectively, and Te-1 and Te-2 decreased by 53 ± 4 and 33 ± 7%, respectively. During unloaded breathing, 60 pmol baclofen prolonged Ti by 120 ± 11% and left Te unaffected. Baclofen abolished vagally mediated changes in Te. On the other hand, the Ti increases caused by either airway occlusion (24 ± 8%) or Ptr of −5 cmH2O (Ti-1; 16 ± 5%) were still significant, but Ti-1 and Ti-2 were not different. A GABAB receptor antagonist, CGP-35348 (2.8 nmol), reversed these effects of baclofen. These results imply that stimulation of GABAB receptors attenuates but does abolish vagally mediated control of Ti. The difference in effects of baclofen on the central and vagal control of Ti and Te suggests different distribution of GABAB receptors in neuronal networks controlling each of these respiratory phases.
Impeding O2 unloading in muscle delays oxygen uptake response to exercise onset in humans
Authors: Hayashi Naoyuki , Ishihara Mutsuhisa , Tanaka Ayumu , Yoshida Takayoshi
Published: December 2017

We tested whether the leftward shift of the oxygen dissociation curve of hemoglobin with hyperpnea delays the oxygen uptake (V˙o 2) response to the onset of exercise. Six male subjects performed cycle ergometer exercise at a work rate corresponding to 80% of the ventilatory threshold (VT) V˙o 2 of each individual after 3 min of 20-W cycling under eupnea [control (Con) trial]. A hyperpnea procedure (minute ventilation = 60 l/min) was undertaken for 2 min before and during 80% VT exercise in hypocapnia (Hypo) and normocapnia (Normo) trials. In the Normo trial, the inspired CO2 fraction was 3% to prevent hypocapnia. The subjects completed two repetitions of each trial. To determine the kinetic variables ofV˙o 2 and heart rate (HR) at the onset of exercise, a nonlinear least-squares fitting was applied to the data averaged from two repetitions by a monoexponential model. The end-tidal CO2 partial pressure before the onset of exercise was significantly lower in the Hypo trial than in the Con and Normo trials (22 ± 1 vs. 38 ± 3 and 36 ± 1 mmHg, respectively, P < 0.05). The time constant ofV˙o 2 and HR was significantly longer in the Normo trial (28 ± 7 and 39 ± 18 s, respectively) than in the Con trial (21 ± 7, 34 ± 16 s, respectively, P < 0.05). TheV˙o 2 time constant of the Hypo trial (37 ± 12 s) was significantly longer than that of the Normo trial, although no significant difference in the HR time constant was seen (Hypo, 41 ± 28 s). These findings suggested that respiratory alkalosis delayed the kinetics of oxygen diffusion in active muscle as a result of the leftward shift of the oxygen dissociation curve of hemoglobin. This supports an important role for hemoglobin-O2 offloading in setting the V˙o 2 kinetics at exercise onset.
Body fluid expansion is not essential for salt-induced hypertension in SS/Jr rats
Authors: Qi Nianning , Rapp John P. , Brand Paul H. , Metting Patricia J. , Britton Steven L.
Published: December 2017

To evaluate the importance of volume in the development of hypertension in inbred Dahl salt-sensitive rats (SS/Jr), we measured the changes in blood pressure (BP) that occurred with oral intake of food (salt) and water in rats whose body weight was permitted to increase versus those in which body weight was maintained constant with a servo-control system. We hypothesized that if volume expansion is essential in the development of hypertension, then BP would not increase if body weight was held constant. We found that oral presentation of chow containing 4% salt to SS/Jr rats caused BP to increase 32.2 ± 2.9 mmHg over 4 days when body weight was controlled at its initial value. Plasma sodium increased from 142.0 to 145.2 meq/l during 4 days of high salt. Neither plasma volume, hematocrit, nor central venous pressure changed significantly on the high-salt diet. In contrast, the inbred Dahl salt-resistant rats (SR/Jr) did not increase their BP during body weight control when given 4% salt. This demonstrates that volume expansion is not an obligatory step in the pressure response to increased salt in SS/Jr rats. Our results obtained with oral presentation of salt, in contrast to intravenous, represent a physiological evaluation of the significance of volume changes in response to dietary salt because no potential regulatory reflexes have been bypassed.
Circadian regulation of chick electroretinogram: effects of pinealectomy and exogenous melatonin
Authors: McGoogan Jennifer M. , Cassone Vincent M.
Published: December 2017

Melatonin is an important component of the avian circadian system. This study investigates the effects of pinealectomy (Pin-X) and melatonin implantation (Mel) on electroretinogram (ERG) rhythms in chicks. Feeding rhythms were monitored to obtain a phase reference for ERG recordings. Pin-X and Mel had little or no effect on feeding rhythms. Sham-operated Pin-X and vehicle implantation had no effect on ERG rhythms in the light-dark (LD) cycle or constant darkness (DD). ERG a- and b-wave amplitudes were higher during the day than during the night. The a- and b-wave implicit times were shorter during the day than during the night. a-Wave sensitivity was higher during the night than during the day, whereas b-wave sensitivity was not rhythmic. Pin-X abolished the circadian rhythm of b-wave amplitude and implicit time in DD but had no effect on a-wave rhythmicity. Mel abolished the rhythm of b-wave amplitude and of a- and b-wave implicit time in DD. Neither treatment affected ERG in LD. These results suggest that the circadian system regulates rhythmic visual function in the retina at least partially through Mel. The role played by the pineal gland and Mel may be specific to some physiological modalities (e.g., vision) while not influencing others (e.g., feeding).
Oxytocin-induced renin secretion in conscious rats
Authors: Huang Wan , Sjöquist Mats , Skott Ole , Stricker Edward M. , Sved Alan F.
Published: December 2017

Arterial hypotension and hypovolemia are known to stimulate neurohypophysial secretion of oxytocin (OT) in rats, although the physiological function of OT under these circumstances is uncertain. We now report that OT infused intravenously into conscious rats at 125 ng ⋅ kg−1 ⋅ h−1, a dose selected to mimic plasma OT levels during hypotension or hypovolemia, increased plasma renin concentration and plasma renin activity by twofold. This effect was prevented by systemic pretreatment with an OT receptor antagonist {[1-(3-mercaptopropionic acid)-2- O-ethyl-d-Tyr-Thr4-Orn8]-OT}. The OT antagonist did not block renin secretion induced by systemic injection of the β-adrenergic receptor agonist isoproterenol, indicating that the OT antagonist does not interfere nonselectively with renin release. Pretreatment of rats with the β-adrenergic receptor antagonist nadolol also prevented OT-induced renin secretion. Similarly, nadolol injected during infusion of OT markedly reduced the elevated plasma renin levels. These observations raise the possibility that pituitary OT secretion during hypotension or hypovolemia in rats may serve to support blood pressure by enhancing activation of the renin-angiotensin system via a β-adrenergic receptor-dependent mechanism.
The neurosteroid allopregnanolone modulates oxytocin expression in the hypothalamic paraventricular nucleus
Authors: Blyth Brian J. , Hauger Richard L. , Purdy Robert H. , Amico Janet A.
Published: December 2017

Virgin, ovariectomized rats exposed to 2 wk of sequential estradiol (E2) and progesterone (P) followed by P withdrawal have increased hypothalamic oxytocin (OT) mRNA and peptide levels relative to sham-treated animals. This increase is prevented if P is sustained. In the central nervous system, P is metabolized to the neurosteroid allopregnanolone (3α-hydroxy-5α-pregnan-20-one), which exerts effects by acting as a positive allosteric modulator of GABAA receptor/Cl−-channel complexes. In the present study, ovariectomized rats that received sequential E2 and P for 2 wk followed by P withdrawal were administered allopregnanolone at the time of P withdrawal. Hypothalamic and plasma allopregnanolone concentrations, serum E2 and P concentrations, and hypothalamic OT mRNA levels were measured at death. Steroid-induced increases in OT mRNA were attenuated in animals treated with allopregnanolone at the time of P withdrawal. The results suggest that allopregnanolone plays an important modulatory role in steroid-mediated increases in hypothalamic OT.
Effects of metabolism and anesthesia on pulmonary ventilation
Authors: Ramsay A. G.
Published: December 2017

Pulmonary ventilation and oxygen consumption of three groups of cats, anesthetized, decerebrated and anesthetized decerebrate, were measured before and after metabolic stimulation by 2:4-dinitrophenol. It was found that anesthesia does not alter quantitatively the respiratory response to an increase in metabolism. Comparison with earlier data shows that a unit increase in oxygen consumption produces a similar response in ventilation in man, dogs and cats, anesthetized or normal. This finding supports the theory that the muscles embody ‘metaboreceptors’ sensitive to metabolic activity which stimulate respiration in exercise. It is postulated that the classical ‘blood-gas’ control of breathing is of minor importance under normal conditions and that the variations in ventilation required during light and moderate exercise are brought about by neural mechanism only.

Submitted on June 30, 1958
Use of Triton X-100 as a hemolytic agent in the spectrophotometric measurement of blood O2 saturation
Authors: Deibler Gladys E. , Holmes Mary S. , Campbell Phyllis L. , Gans June
Published: December 2017

A spectrophotometric method for the measurement of blood O2 saturation utilizing Triton X-100 as the hemolytic agent is described. The results of its comparison with the standard manometric method indicate that it provides reliable values for blood O2 saturation. Triton X-100 was found to be a more suitable hemolytic agent than saponin. A nomogram is presented which facilitates the calculation of percentage of O2 saturation from the measurements required by the method.

Submitted on August 27, 1958
Pattern of N15-excretion in man following administration of N15-labeled L-phenylalanine
Authors: Wu Hsien , Sendroy Julius
Published: December 2017

On the basis of the same dose (in mEq) per unit body weight of N15 administered, the patterns of N15-excretion following oral administration of labeled L-phenylalanine and of ammonium citrate have been compared with those of labeled glycine and aspartic acid in previous studies. In the first few hours, the patterns for ammonia, urea and hippuric acid are markedly different for different amino acids. After 6–8 hours, with the exception of hippuric acid, the patterns are substantially the same, regardless of the particular amino acid administered. The data obtained in the first few hours reflect predominantly the rate of metabolism of the particular amino acid administered. The ratios of the isotope concentration of glycine (calculated from that of hippuric acid) to that of ammonia, following the oral administration of l-phenylalanine, and of ammonium citrate, deviate from theory not only in the early stages of excretion, but in the attainment of a final value of about 0.6; this indicates the possibility that the turnover rate of glycine is higher than the average for ammonia-forming amino acids. Following oral administration of L-phenylalanine and also after ammonium citrate, the isotope concentrations of ammonia and of urea are equal at the maximum point of the latter. From the ammonia-urea relationship, the assumption of a single pool of amino acids in the body seems justified in oral experiments.

Note:

(With the Assistance of James George and Daisy Yen Wu)

Submitted on September 15, 1958
Vascular convection of heat from active muscle to overlying skin
Authors: Cooper Theodore , Randall Walter C. , Hertzman Alrick B.
Published: December 2017

Both thermocouple and radiometer measurements revealed marked elevations in temperature of skin immediately over actively working muscles of the forearm and leg. Such localized increases in the surface temperature were confined to skin overlying rhythmically contracting muscle. They were attributed to a direct vertical vascular convection of heat from the muscle to the overlying skin because they were prevented by blocking perfusion or by surgical severance of skin from underlying tissue and because of the character of the temperature gradient in the intervening tissue. The argument for a venous rather than an arterial convection was based on a) the effects of compression of the superficial veins on the temperature changes, b) the absence of effect on the latter by electrophoresis of adrenaline into the skin, which greatly reduced arterial perfusion of the skin, c) the absence of evidence of arterial dilation in the skin and d) the lack of relation of the location of arterial twigs to the topography of the temperature rise.

Submitted on August 11, 1958
Dose-response relationships of human urinary erythropoietin
Authors: Garcia Joseph F. , Van Dyke Donald C.
Published: December 2017

The response to graded doses of human urinary erythropoietin was determined in normal, hypophysectomized and fasted rats by use of the Fe59 red cell incorporation assay. In all three cases a highly significant correlation between the red cell incorporation of radioiron and the dose of erythropoietin administered was observed. Also, total red cell volumes and total circulating hemoglobins determined after 14 daily injections of erythropoietin to normal rats showed the presence of polycythemia. At the highest dose administered, the degree of polycythemia was similar to that obtained in rats exposed to a simulated altitude of 20,000 feet for 14 days. The value of the Fe59 red cell incorporation assay as an assay for erythropoietin was substantiated by the high correlation observed between the increase in total circulating hemoglobin and radioiron incorporation into red cells.

Submitted on August 18, 1958
Diffusion of liquid water through human skin
Authors: Buettner Konrad J. K.
Published: December 2017

A human foot exposed to water takes in 1–2 gm of water per hour. A small portion of this uptake is imbibed by the stratum corneum, the major portion seems to enter the system. The transfer has been observed for periods exceeding 50 hours. With increasing salinity less water is taken in until, in a 2 molar solution, transfer ceases. Stronger solutions draw water out of the skin. Similar facts are observed for hands and arms. For explanation an active process in the skin is proposed.

Submitted on August 25, 1958
Diffusion of water vapor through small areas of human skin in normal environment
Authors: Buettner Konrad J. K.
Published: December 2017

Four small skin areas of the forearm were exposed concurrently to four small bottles at skin temperature. The bottles contained certain wet salts which condition the local vapor pressure. The vapor transfer between skin and bottles resulted in a measurable weight change of the bottles. One thousand tests on 250 people were made in a comfortable room. Below a critical humidity, vapor left the skin; above this ‘neutral relative humidity’ (NRH) the skin gained vapor. A small portion of this skin intake is used to moisten the horny layer. Correcting for this, the average of all tests is NRH = 86%. Frequency curves show two significant maxima besides that around 86%, viz. one around a NRH of 60–70%, generally concurrent with edema, and one above 90% NRH, usually observed on sweating skin. Length of exposure (30 min.-8 hr.), season and skin temperature (excluding sweating) have no recognizable influence on NRH.

Submitted on August 25, 1958
Changes in acid-base balance and blood gases during muscular activity and recovery
Authors: De Lanne R. , Barnes J. R. , Brouha L. , Massart F.
Published: December 2017

Changes in the blood gases and acid-base balance during muscular work and recovery were investigated for males and females under various controlled environmental conditions. Changes in venous blood oxygen and carbon dioxide are influenced both by the intensity and duration of the exercise and by the environmental temperature. The pH of the blood is similarly affected. The direct measurement of pH was found to be a better index of the variation in the acid-base balance than the pH calculated from Henderson's equation at a fixed CO2 pressure. Lactic acid in the blood is, like the blood gases, influenced by ambient conditions, but is more closely related to the intensity than to the duration of the exercise.

Submitted on October 28, 1958
Finger numbness and temperature in Antarctica
Authors: Massey P. M. O.
Published: December 2017

A group of new arrivals in Antarctica and a group staying a second consecutive year were observed over a period of one year. Differences of cold acclimatization in finger sensitivity was demonstrated which were lost within 6 weeks. There was no difference in resting finger temperature between the groups, but there was a significant fall in temperature over the year. It was concluded that some forms of acclimatization to cold occur only after a greater degree of cold stress than do others. Second year men showed the greater immunity to frostbite under the experimental conditions, but this was not proved statistically. The addition of drift snow to the ‘cold’ wind doubled the numbness induced in the finger. Under ‘very cold’ conditions drift increased finger numbness over six times. Provided sufficient time is spent outdoors, the outdoor temperature is the more important for cold acclimatization, regardless of comfortable indoor temperatures.

Submitted on July 21, 1958
Pulmonary resistance and state of inflation of lungs in normal subjects and in patients with airway obstruction
Authors: Cheng Tsung O. , Godfrey Malcolm P. , Shepard Richard H.
Published: December 2017

The relationship between pulmonary resistance and the state of inflation of the lung was estimated throughout the expired vital capacity, using the multiple interrupter of Clements and Elam and a servo-spirometer. In normal subjects the pulmonary resistance was lowest near full inflation and remained relatively constant until about 80% of the vital capacity had been expired. It then rose abruptly and approached infinity at full expiration. In patients with obstructed airways, this relationship was altered in one of several ways: 1) normal resistance near full inflation increasing to high levels early in the expired vital capacity, 2) high resistance near full inflation with little further rise until late in expiration and 3) various combinations of the above. The first pattern probably reflects changes in the small, relatively flaccid airways while the second pattern probably reflects changes in the large, relatively rigid airways or in pulmonary viscous resistance. The type of relationship between resistance and lung volume also appears to influence the partition of the total lung capacity.

Submitted on February 17, 1959
CO2 diuresis, with special reference to role of the left atrial stretch receptor mechanism
Authors: Valtin H. , Wilson I. D. , Tenney S. M.
Published: December 2017

Co2 diuresis is probably mediated via a nonosmotic influence on the supraopticohypophyseal system. Since the left atrial stretch receptor mechanism is one such nonosmotic system which Co2 might influence, experiments were designed to elucidate its role. It was found that Co2 diuresis may be abolished by the erect posture or by applying tourniquets high on the thighs while supine, and that it may be restored by standing in a tank of water or by mild exercise. Increases in plasma volume, total blood volume, or pulmonary blood volume, which conceivably might stretch the left atrium, did not occur during Co2 diuresis. Voluntary hyperventilation mimicking that which accompanies Co2 inhalation resulted in a much smaller diuresis and one which, unlike that of Co2, was accompanied by increased sodium excretion. Maintaining normal alveolar Co2 tension during voluntary hyperventilation by simultaneous inhalation of 2% Co2 in no way altered this result. Bilateral vagus section does not abolish Co2 diuresis, but may enhance it. It is concluded, therefore, that the left atrial stretch receptor mechanism is not the afferent system for Co2 diuresis.

Submitted on January 26, 1959
Effect of time after feeding and carbohydrate or water supplement on work in dogs
Authors: Young D. R. , Iacovino A. , Erve P. , Mosher R. , Spector H.
Published: December 2017

Effects of proximity of the last meal and post-absorptive supplementation with water or carbohydrate were examined in reference to aerobic work performance in the dog. In the first series, performance was measured utilizing a standard 40-minute period of treadmill running adjusted to a work load of 202.9 kg-m/min. administered 1 ½, 4, 6 and 24 hours following the intake of a normal meal. On the average, minute pulse rate was significantly nine beats higher and body temperature 0.75°F higher at 4 and 6 hours following the meal. There was no significant effect on energy expenditure due to specific dynamic action of the food. Maximum aerobic work capacity was studied. Provision of 1.5 liters of water during work markedly improved (+80%) performance, whereas provision of carbohydrate just prior to work was without immediate benefit. Increased work capacity due to water supplementation is mediated by the maintenance of a relatively normal state of hydration, improvements in temperature regulation and a beneficial effect on carbohydrate metabolism.

Submitted on April 2, 1959