bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal hiccups in the baboon
Authors: Stark R. I. , Daniel S. S. , Garland M. , Jaille-Marti J. C. , Kim Y. I. , Leung K. , Myers M. M. , Tropper P. J.
Published: December 2017

Bouts of hiccuping are recognized by pregnant women as distinct episodic movements of their fetuses. Ultrasound imaging of these fetuses has documented the occurrence of hiccups from early gestation through parturition. This study provides a systematic characterization of prenatal hiccuping in the fetal baboon (Papio species). Tracheal fluid pressure was recorded from 11 chronically instrumented fetal baboons for 21.5 +/- 7.3 consecutive days (mean +/- SD) over a range in gestation from 124 to 164 days (term 175 days). In an initial review of pressure recordings by visual inspection, hiccups were recognized as distinctive high-amplitude fluctuations in tracheal pressure that were readily discriminated from fetal breaths. Automated techniques were then developed and validated to detect hiccups and summarize their features. The mean hiccup amplitude was 23.0 +/- 3.1 mmHg, inspiratory time was 0.26 +/- 0.03 s, and expiratory time was 0.27 +/- 0.02 s. Each of these features discriminated hiccups from breaths (P < 0.001). Hiccuping incidence (1.8 +/- 0.4% of time), rate (26.2 +/- 6.2 min-1), bout duration (4.3 +/- 0.8 min), and the interval between bouts (3.35 +/- 0.60 h) were also different (P < 0.01) from breathing. These features of hiccups remained relatively constant over the latter third of gestation with the exception of an increase in duration of the expiratory time interval (r = 0.54, P < 0.01). Despite their vigorous nature, bouts of hiccuping were not associated with transitions in behavioral state. Moreover, the features of hiccups were not differentiated by state. Bouts of hiccuping recurred in a cyclic fashion, on average every 3-4 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Hormonal, renal, and metabolic alterations during hypertension induced by chronic inhibition of NO in rats
Authors: Navarro J. , Sanchez A. , Saiz J. , Ruilope L. M. , Garcia-Estan J. , Romero J. C. , Moncada S. , Lahera V.
Published: December 2017

The evolution of renal excretory function and circulating vasoactive systems was studied during progressive increases in blood pressure (BP) induced in rats by oral administration of NG-nitro-L-arginine methyl ester (L-NAME; 5-30 mg/100 ml) for 5 wk. L-NAME induced a stepped elevation (P < 0.05) in BP levels without changing creatinine clearance, urine flow, or sodium excretion rate along the study. Reductions (P < 0.05) in plasma renin activity and plasma aldosterone concentration were found only during treatment with 30 mg/100 ml of L-NAME. Plasma norepinephrine and epinephrine concentrations were elevated (P < 0.05) in the last week of the study. Plasma concentrations of endothelin-1 and urinary excretion of prostaglandin E2, 6-ketoprostaglandin F1 alpha, and thromboxane B2 were not significantly affected by L-NAME. Similarly, no changes in plasma concentrations of glucose, insulin, total cholesterol, or triglycerides were observed. In summary, during long-term administration of L-NAME, progressive increases in BP levels were observed without changes in either sodium excretion or enhanced circulating vasoconstrictor activity. Thus, it is likely that inhibition of synthesis of nitric oxide (NO) in the vasculature leads to an imbalance between the tonic relaxing action of NO and the influences of vasoconstrictor agents even when the latter remain at normal levels.
Hydrops fetalis in nephrectomized fetal lambs infused with angiotensin I
Authors: Faber J. J. , Anderson D. F.
Published: December 2017

Nine bilaterally nephrectomized fetal sheep were infused for 6 days with angiotensin I in sterile water, and five nephrectomized fetal sheep were infused for 6 days with water alone. Total dose of angiotensin was 13.8 +/- 8.6 (SD) mg/kg fetal dry wt, and the total volumes of infused water were 303 +/- 201 and 423 +/- 164 ml, respectively. Of the fetuses infused with angiotensin I, one was of normal appearance, two showed moderate hydrops fetalis, and the remaining fetuses were grossly hydropic. All water-infused fetuses were normal. Their wet-to-dry weight ratios were 7.98 and 6.36 (P < 0.015), representing a 25% of normal body weight excess of water in the angiotensin I-infused fetuses. Six days of angiotensin I infusion caused a gradual rise in fetal arterial blood pressure from 37 +/- 15 to 81 +/- 15 mmHg (P < 0.05) and a gradual rise in venous blood pressure from 2.7 +/- 1.0 to 10.5 +/- 1.7 mmHg (P < 0.05). It was concluded that the fetal edema was due to the elevation in venous pressure. Plasma concentrations of Na+, K+, Cl-, HCO3-, total alpha-amino acids, fructose, glucose, and lactate in the fetus and the ewe did not identify an osmotically active solute responsible for the transplacental attraction of excess water into the conceptus, and the mechanism that attracted this excess water across the placenta remains unclear.
Nifedipine inhibits adrenal but not circulating catecholamine response to nicotinic stimulation in dogs
Authors: Gaspo R. , Yamaguchi N. , de Champlain J.
Published: December 2017

We investigated whether dihydropyridine-sensitive L-type Ca2+ channels are implicated in adrenal and sympathetic neural catecholamine release in response to nicotinic stimulation by 1,1-dimethyl-4-phenylpiperazinium (DMPP), a selective cholinergic nicotinic agonist, in dogs anesthetized with pentobarbital sodium. Plasma epinephrine and norepinephrine concentrations were measured in adrenal venous and aortic blood by a high-performance liquid chromatography-electrochemical method. In the vehicle control group, intravenous injection of DMPP (15 micrograms/kg iv) produced a significant increase in adrenal venous catecholamine output and aortic catecholamine concentration. These increasing responses were highly reproducible on the repetition of DMPP injection given 30 min after the first injection. In dogs receiving nifedipine (100 micrograms/kg iv), the net increase in adrenal venous epinephrine and norepinephrine output in response to DMPP was attenuated by 42% (P < 0.05), while no significant changes were observed in the aortic catecholamine response to DMPP. In dogs treated with pentolinium (1 mg/kg iv), both adrenal epinephrine and norepinephrine responses to DMPP were inhibited by 67% (P < 0.05) and 84% (P < 0.05), respectively. Furthermore, pentolinium inhibited aortic catecholamine response to DMPP by > 95% (P < 0.05). The present study suggests that DMPP-induced release of adrenal catecholamines was mediated, at least in part, through mechanisms involving dihydropyridine-sensitive L-type Ca2+ channels under in vivo conditions. By contrast, however, the results also suggest that dihydropyridine-sensitive L-type Ca2+ channels were not implicated in the neurotransmission at the level of sympathetic ganglions.
Seasonal and temperature-induced changes in myosin heavy chain composition of crucian carp hearts
Authors: Vornanen M.
Published: December 2017

Myosin heavy chain isoforms of the ventricular myocardium from crucian carp (Carassius carassius L.) hearts were analyzed in different times of the year by gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis [K. A. Esser, M. O. Boluyt, and T. P. White, Am. J. Physiol. 255 (Heart Circ. Physiol. 24): H659-H663, 1988]. In winter only one myosin heavy chain type was present, but in summer about one-half of the winter myosin was replaced by more slowly moving summer myosin. The occurrence of summer myosin correlated with seasonal changes in water temperature of the pond, where the fish were caught. Furthermore, the heavy chain composition of the heart was altered by temperature acclimation in the laboratory: cold-acclimated (2 degrees C) fish had only winter myosin, but warm-acclimated (22 degrees C) fish had both summer and winter myosin in about equal amounts. Myosin adenosinetriphosphatase activity of the hearts containing both summer and winter myosin was higher than that of hearts containing only winter myosin. Functionally, changes in myosin heavy chain composition were associated with inverse thermal acclimation in the heart rate. Warm-acclimated fish had higher in vitro heart rate and shorter contraction duration than cold-acclimated animals. Present findings suggest that changes in myosin heavy chain composition together with concomitant changes in Ca2+ activation of contraction make possible large seasonal alterations in the activity of crucian carp hearts. These adjustments are needed to adapt the cardiovascular system to winter hibernation and summer activity, which are dictated by seasonally bound changes in environmental conditions.
Essential fatty acid deficiency impairs the responsiveness of renal pelvic sensory receptors
Authors: Kopp U. C. , Farley D. M. , Smith L. A. , Knapp H. R.
Published: December 2017

The role of prostaglandins in renal sensory receptor activation was examined in rats fed an essential fatty acid-deficient (EFAD) diet to cause tissue arachidonate depletion. Littermates fed a standard diet were used as controls. In anesthetized rats, the increases in afferent renal nerve activity due to increasing ureteral pressure 2.5, 5, 7.5, 10, 12.5, and 15 mmHg were significantly reduced by the EFAD diet (P < 0.02): 3 +/- 5, 3 +/- 5, 11 +/- 5, 9 +/- 5, 19 +/- 3, and 17 +/- 5%, respectively, in EFAD rats and 23 +/- 11, 36 +/- 15, 50 +/- 15, 52 +/- 8, 72 +/- 17, and 90 +/- 19%, respectively, in control rats. In EFAD rats, addition of prostaglandin E2 (PGE2) to the renal pelvic perfusate restored the afferent renal nerve activity response to increased ureteral pressure toward that in control rats. PGE2 had no effect in control rats. Also the afferent renal nerve activity responses to renal pelvic perfusion with bradykinin at 4, 20, 100, and 500 micrograms/ml were significantly suppressed by the EFAD diet (P < 0.01): 13 +/- 15, 5 +/- 7, 60 +/- 19, and 63 +/- 20%, respectively, in EFAD rats and 122 +/- 23, 142 +/- 31, 172 +/- 19, and 190 +/- 39%, respectively, in control rats. These results demonstrate an important role for arachidonate metabolites, particularly PGE2, in renal sensory receptor activation. Together with our previous studies showing that indomethacin blocks the afferent renal nerve activity responses to increased ureteral pressure or bradykinin, the present studies provide strong evidence for an essential role of prostaglandins in renal sensory receptor activation.
Corticosterone decreases nonshivering thermogenesis and increases lipid storage in brown adipose tissue
Authors: Strack A. M. , Bradbury M. J. , Dallman M. F.
Published: December 2017

Brown adipose tissue (BAT) contains glucocorticoid receptors; glucocorticoids are required for maintaining differentiated BAT in culture. These studies were performed to determine the effects of corticosterone on BAT thermogenic function and lipid storage. Rats were adrenalectomized and given subcutaneous corticosterone pellets in concentrations that maintained plasma corticosterone constant across the range of 0-20 micrograms/dl or were sham adrenalectomized. All variables were examined 5 days after surgery and corticosterone replacement. Measures of BAT function-thermogenic capacity [guanosine 5'-diphosphate (GDP) binding and uncoupling protein (UCP; a BAT-specific thermogenic protein)] and storage (BAT wet wt, protein, and DNA levels) were made. Plasma hormones (corticosterone, adrenocorticotropic hormone, insulin, 3,3',5-triiodothyronine, and thyroxine were measured. Corticosterone significantly affected BAT thermogenic measures: UCP content and binding of GDP to BAT mitochondria decreased with increasing corticosterone; GDP binding characteristics in BAT from similarly prepared rats examined by Scatchard analysis showed that maximum binding (Bmax) and dissociation constant (Kd) decreased with increasing corticosterone dose. BAT DNA was increased by adrenalectomy and maintained at intact levels with all doses of corticosterone; BAT lipid storage increased dramatically at corticosterone values higher than the daily mean level in intact rats. Histologically, the number and size of lipid droplets within BAT adipocytes increased markedly with increased corticosterone. White adipose depots were more sensitive to circulating corticosterone concentrations than were BAT depots and increased in weight at levels of corticosterone that were at or below the daily mean level of intact rats. We conclude that, within its diurnal range of concentration corticosterone acts to inhibit nonshivering thermogenesis and increase lipid storage.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of ultradian and circadian oscillations of carbon dioxide production by various endotherms
Authors: Stupfel M. , Gourlet V. , Perramon A. , Merat P. , Putet G. , Court L.
Published: December 2017

Carbon dioxide emission (VCO2) was computed every 20 min from continuous CO2 concentration recordings taken during 3-30 consecutive days, in strictly controlled environmental conditions, in 54 OF1 mice, 99 Japanese quail, 66 Sprague-Dawley rats, 50 Hartley guinea pigs, 7 chicks, for 7-15 days on 2 Cynomolgus monkeys, and for 24 h on 7 premature infants. This VCO2 shows circadian and ultradian oscillations that were analyzed for frequencies and amplitudes in light-dark 12-h alternation (LD 12:12), continuous light (LL), and continuous dark (DD). Circadians were not always identified or were often masked in LL or DD (mostly in guinea pigs, quail, and rats), while ultradians (tau > or = 40 min) were found in all species, at every time, and in all light regimens. Analysis of variance and chi 2 show significant (P < 0.001) interspecies differences for ultradian (1.07 < tau < 1.40 h) intervals and for circadian and ultradian VCO2 amplitudes. Relationships between ultradian and circadian VCO2 oscillations differ according to the species, ultradians appearing as an entity characteristic for each endotherm species.
Presence of insulin-like growth factor I but absence of the binding proteins in the bile of rats
Authors: Kong W. , Philipps A. F. , Dvorak B. , Anderson G. G. , Lake M. , Koldovsky O.
Published: December 2017

Whereas insulin-like growth factor I (IGF-I) has been found in various body fluids from different species, the presence or absence of IGF and associated binding proteins (IGFBPs) in bile has not been clearly defined. Bile concentration of IGF-I was measured in this study and found to be highest in the neonate and lowest in adult rats [133 +/- 15.9, 79.4 +/- 10.5, 45.3 +/- 12.7 ng/ml (mean +/- SE) in 12-day-old, 33-day-old, and adult rats, respectively]. When bile delivery rates of IGF-I (i.e., the product of IGF-I concentration in bile and the biliary flow rate) were calculated, IGF-I delivery was highest in weanling rats (469 pg.h-1.g body wt-1). When expressed as amount of IGF-I in bile delivered per day, however, delivery rates rose from 0.2 micrograms/day in the suckling and remained constant at 1.6-1.7 micrograms/day in both weanling and adult animals. Bile samples exposed to a placental membrane IGF receptor preparation showed significant dose-dependent inhibition of binding of native IGF-I. Because no IGF binding proteins were identified by Western ligand blot or by Sephadex gel chromatography, the results suggest the presence of biologically significant quantities of bioactive IGF-I in bile. We speculate that IGF-I in bile may play an important role in the growth of the gastrointestinal tract, both in the suckling as well as later in life.
Factors affecting the sensitivity of the lingual trigeminal nerve to acids
Authors: Bryant B. P. , Moore P. A.
Published: December 2017

Oral sensitivity to acids mediates a range of irritation, from desirable sensations of pungency in various foods and beverages to the pain associated with harmful levels of acidity and inflammation. To characterize the role of the epithelial and vascular processes in neural sensitivity to acid applied to the lingual mucosa, we measured lingual trigeminal nerve responses in rats to acidic stimuli of varying physicochemical properties. Stimulatory efficacy was strongly correlated with lipophilicity (octanol-H2O partition coefficient) for the series of straight-chain fatty acids from one to six carbons. Neither acid dissociation constant nor the pH of stimulus solutions correlated with stimulatory efficacy for the fatty acids and six other organic acids. The hypothesis that weakly acidic stimuli gain access to trigeminal nerve endings primarily through the lipid phase of the epithelium was supported by these findings. Further support for this hypothesis is the result that LaCl3, an inhibitor of epithelial tight junctions, had no effect on the neural response to n-pentanoic acid. The potential relevance of buffering-clearance in modulating responses to acid was indicated by the finding that the application of 1 mM capsaicin to the tongue reversibly inhibited the neural response to acid, as well as causing plasma extravasation in lingual epithelium.
Osmolality-induced changes in aldosterone secretion involve a chloride-dependent process
Authors: Hayama N. , Wang W. , Schneider E. G.
Published: December 2017

Alterations in extracellular osmolality have a powerful inverse effect on aldosterone secretion that is associated with sustained changes in cell volume. With dispersed bovine glomerulosa cells grown in primary culture, the effects of alterations in osmolality on cell volume measured by the distribution of [14C]urea and [3H]mannitol were determined in the presence and absence of chloride. In the presence of chloride, decreases in osmolality increased cell volume, whereas angiotensin II (< 4 x 10(-9) M) did not affect cell volume. When chloride was removed from the medium (replacing chloride with the impermeant methyl sulfate ion), cell volume decreased significantly, but basal aldosterone secretion was not altered. In the absence of chloride, the increases in cell volume, cytosolic calcium concentration, and aldosterone secretion induced by decreases in osmolality were significantly suppressed. The replacement of chloride with the methyl sulfate ion suppressed the increases in both cytosolic calcium concentration and aldosterone secretion induced by low (< 4 x 10(-9) M) but not high (4 x 10(-8) M) concentrations of angiotensin II. The results suggest that reductions in osmolality increase cell volume, partly by inducing an influx of chloride ions that contributes to the total net influx of water. Reductions in cell volume caused by an increase in osmolality or by replacing the chloride ion with the impermeant methyl sulfate ion may induce alterations in membrane stretch that may decrease the angiotensin II-induced increase in cytosolic calcium concentrations, which in turn suppresses aldosterone secretion.
Oxygen, glucose, and lactate uptake by fetus and placenta during prolonged hypoxemia
Authors: Hooper S. B. , Walker D. W. , Harding R.
Published: December 2017

Our aim was to compare the effects of short (4 h) and prolonged (24 h) periods of reduced uterine blood flow (RUBF) on fetal and placental uptake of O2, glucose, and lactate. In pregnant sheep, uterine and umbilical blood flows were measured under normal conditions and after 4 and 24 h of RUBF. A 50% reduction in uterine blood flow caused a 56% reduction in fetal arterial O2 saturation (SaO2). Umbilical blood flow increased from 325 +/- 33 to 378 +/- 32 ml.min-1.kg-1 (P < 0.05) after 4 h but was not different from pre-RUBF values after 24 h. O2 uptake by the gravid uterus was not altered by RUBF, due to an increase (84%) in uterine O2 extraction. Similarly, uteroplacental and fetal O2 consumptions and fetal glucose uptake were not affected by RUBF, whereas uteroplacental glucose uptake was significantly reduced after 4 h (by 42%) and 24 h (by 58%) of RUBF. Fetal lactate uptake was greatly reduced from 78.7 +/- 15.5 to -167 +/- 57 mumol.min-1.kg-1 after 4 h and to -198 +/- 80 mumol.min-1.kg-1 after 24 h of RUBF; negative values indicate placental lactate uptake from the fetal circulation. Thus, although RUBF significantly reduced fetal SaO2, fetal and uteroplacental O2 consumptions did not change. In addition, although fetal glucose uptake was not altered by RUBF, during RUBF the placenta became a major site of lactate clearance from the fetal circulation.
Altered vagal and sympathetic control of heart rate in left ventricular dysfunction and heart failure
Authors: Kinugawa Toru , Dibner-Dunlap Mark E.
Published: December 2017

We investigated alterations in autonomic control of heart rate in conscious dogs with left ventricular (LV) dysfunction in the presence and absence of heart failure (HF) due to rapid pacing. In dogs with LV dysfunction but no HF, indexes of parasympathetic control decreased significantly after only 4 days of pacing. In dogs with fully developed HF, both vagal and sympathetic contributions were small. Vagomimetic doses of atropine increased both R-R interval (419 ± 25 to 466 ± 34 ms, P < 0.05) and standard deviation (SD) of the R-R interval (13 ± 2 to 34 ± 9 ms, P < 0.05). The digitalis glycoside deslanoside (Cedilanid-D) alone prolonged R-R interval (420 ± 33 to 492 ± 44 ms, P < 0.01) and tended to increase SD (14 ± 4 to 28 ± 8 ms, P = 0.08). After Cedilanid-D, low-dose atropine resulted in no significant further change in R-R interval or SD. These data indicate that changes in vagal control of heart rate become apparent at a very early developmental stage of LV dysfunction, and we speculate that this may provide important prognostic information in patients who are at risk for developing progressive myocardial dysfunction and HF.

autonomic nervous system; digitalis glycoside; -blockade; low-dose atropine; pacing-induced heart failure

Submitted on March 25, 1994

Accepted on August 17, 1994
Assessment of spontaneous baroreflex sensitivity in rats a new method using the concept of statistical dependence
Authors: Cerutti C. , Ducher M. , Lantelme P. , Gustin M. P. , Paultre C.
Published: December 2017

A new method was developed to evaluate the cardiac baroreflex sensitivity (BRS) from spontaneous mean arterial pressure (MAP) and heart rate (HR) changes in conscious rats. It relies on the determination of the statistical dependence between MAP and HR values. In 13 control rats, 12 rats with a pharmacologically induced hypertension, and 7 rats with a chronic sinoaortic denervation (SAD), dependent (MAP, HR) couples related to the baroreflex activity were selected to determine the spontaneous BRS (Sp-BRS). In control and hypertensive rats, pharmacological BRS (Ph-BRS) was estimated using graded bolus intravenous doses of vasoactive drugs. Ph-BRS was significantly lower in hypertensive than in control rats. Sp-BRS was determined in 10 control and 10 hypertensive rats and was strongly correlated with Ph-BRS (r = 0.83, n = 20, P < 0.0001). Sp-BRS could be evaluated in six SAD rats and was profoundly decreased (-86%, P < 0.001) compared with control rats. In conclusion, this work validates the estimation of the cardiac BRS from spontaneous MAP and HR variations with use of (MAP, HR) couples of values that are statistically dependent.
Seasonal variations of capillary hydraulic conductivity and volume status
Authors: Hargrave R. W. , Huxley V. H. , Thipakorn B.
Published: December 2017

The purpose of this study was to determine whether circulating plasma protein concentration, capillary hydraulic conductivity (Lp), and overall volume status in frogs were correlated and whether these correlations varied with season. Individual vessel Lp was thus examined on a monthly basis and correlated with changes in protein content in three body compartments (blood, lymph, and body cavity) over a 10-yr period. The frogs were anesthetized, blood and fluid samples collected, Lp assessed, and samples assayed for overall protein content. Volume status indicators varied cyclically over the course of 1 yr. Protein levels reached their peak in winter and were lowest in summer for all compartments. Lp for venular and arteriolar capillaries reached maximal levels in summer and fell steadily throughout the remainder of the year. Basal true capillary Lp was stable over the course of the year. Lp and total protein concentration were inversely proportional to each other on a seasonal basis but did not correlate on a monthly basis. Therefore, we conclude that the lack of a simple relationship between Lp and volume status suggests an independent driver such as a hormonal signal for the hydraulic conductivity.
Endotoxin tolerance alters thermal response of guinea pigs to systemic infusions of tumor necrosis factor-alpha
Authors: Roth J. , Zeisberger E.
Published: December 2017

In guinea pigs, intra-arterial infusions of 5 micrograms/kg tumor necrosis factor-alpha (TNF; specific activity 20,000 U/micrograms; duration of infusion 45-50 min) evoked a biphasic elevation of abdominal temperature lasting approximately 6 h. One week after systemic infusion of TNF, the animals started to receive either five intramuscular injections of bacterial lipopolysaccharide (LPS from Escherichia coli; 20 micrograms/kg) or equivalent volumes of solvent (0.9% NaCl) in intervals of 3 days. Fever in response to repeated injections of LPS was progressively attenuated; the animals developed endotoxin tolerance. Repeated injections with solvent did not cause any measurable changes in abdominal temperature. Three days after the fifth injection of LPS or solvent, all animals again received an intra-arterial infusion of 5 micrograms/kg TNF. In guinea pigs injected five times with solvent, the biphasic elevation of abdominal temperature could again be observed in response to systemic infusions of TNF. In endotoxin-tolerant animals, however, only the first peak of the biphasic thermal response lasting approximately 60 min could be monitored after infusions with TNF. The second phase of the thermal response to administration of TNF, which normally lasts > 5 h, was abrogated almost completely. The significant suppression of the febrile response to TNF infusions did not seem to be caused by a more rapid elimination of TNF from the circulation of endotoxin-tolerant guinea pigs. Circulating levels of TNF, measured 60 and 180 min after the start of TNF infusions, were not different before and after development of endotoxin tolerance. In conclusion, the development of endotoxin tolerance in guinea pigs is accompanied by a reduced responsiveness to TNF administered exogenously.
H2 gas clearance technique for separating rat uterine blood flow into endometrial and myometrial components
Authors: Zhang R. S. , Guth P. H. , Scremin O. U. , Chaudhuri G.
Published: December 2017

The H2 gas clearance technique was employed to measure uterine blood flow (UBF) in ovariectomized rats. A needle-type platinum electrode (125 microns diam) was inserted into the rat uterine wall to measure the tissue blood flow surrounding the electrode. The electrode can be placed in individual layers of the uterus to measure the endometrial blood flow (EBF) or the myometrial blood flow (MBF). By use of this technique, baseline EBF and MBF were 37.8 +/- 3.53 (n = 21) and 47.2 +/- 4.56 (n = 5) ml.min-1.100 g-1, respectively, with an EBF/MBF ratio of 0.8. Intravenous bolus injection of 17 beta-estradiol (1 microgram/kg) induced a significant increase in UBF. Phenylephrine, an alpha-adrenergic receptor agonist, reduced UBF. In some animals, a second platinum electrode was used to measure gastric mucosal blood flow simultaneously with UBF. While 17 beta-estradiol selectively increased UBF, pentagastrin selectively increased gastric mucosal blood flow. To further validate the baseline UBF distribution between endometrial and myometrial layers, iodo[14C]antipyrine autoradiography was employed. With the iodo[14C]antipyrine technique, the EBF/MBF ratio was 0.91 +/- 0.07 (n = 5), which is similar to that obtained with the H2 gas clearance technique.
Starvation-induced increase of hepatic alanine uptake is related to changes in sensitivity to SH-group reagents
Authors: Felipe A. , Remesar X. , Pastor-Anglada M.
Published: December 2017

Changes in L-alanine transport in plasma membrane vesicles from livers of control and 24- and 48-h starved adult rats and the sensitivity of alanine uptake to sulfhydryl group reagents [N-ethylmaleimide (NEM) and p-chloromercuribenzenesulfonate (p-CMBS)] were studied. The portal concentration of certain amino acids was measured, and the relationship between L-alanine transport kinetic parameters and amino acid levels was analyzed. Starvation only induced a decrease in portal concentration of these amino acids that are mainly carried by Na(+)-dependent systems (85 and 61% for 24- and 48-h starved rats, respectively). Portal alanine concentration was lower in 24-h starved animals than in control rats (370 vs. 587 microM) and further decreased after 48 h of fasting (228 microM). Starvation induced an increase in maximum velocity (Vmax) values of Na(+)-dependent L-alanine transport (7.19, 8.97, and 12.38 pmol.U 5'-nucleotidase-1.10 s-1 for control and 24- and 48-h starved rats, respectively) with slight, but not significant, changes in the apparent Michaelis constant (Km) values (3.35, 2.63, and 2.20 mM for control and 24- and 48-h starved rats, respectively). Portal alanine showed a directly close correlation with Km values and inverse with Vmax values. The mean affinity constant values for the effects of NEM and p-CMBS on Na(+)-dependent L-alanine transport were lower in 48- (2.57 and 0.13 mM, respectively) and 24-h starved rats (3.59 and 0.32 mM, respectively) than in control rats (8.56 and 0.59 mM, respectively) and showed a directly strong correlation with kinetic characteristics of L-alanine transport and portal alanine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Natriuretic role of endogenous oxytocin in male rats infused with hypertonic NaCl
Authors: Huang W. , Lee S. L. , Sjoquist M.
Published: December 2017

The involvement of endogenous oxytocin (OT) in the renal natriuretic response to an intravenous load of hypertonic and isotonic saline was investigated in anesthetized male rats with use of a selective OT-receptor antagonist [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-OT (OT-ant). NaCl was infused (0.05 mmol.min-1.kg body wt-1 iv for 120 min) as a hypernatremic (HNa) solution or as an isotonic solution producing volume expansion (VE). HNa markedly increased sodium excretion from 0.25 +/- 0.06 to 10.04 +/- 0.62 mumol/min, whereas VE yielded only a moderate increase from 0.25 +/- 0.04 to 1.64 +/- 0.15 mumol/min. The increase in potassium excretion and urine flow rate during HNa was similar to that during VE. There were no significant changes in mean arterial pressure in either case. Administration of OT-ant delayed the natriuresis induced by HNa and reduced it by 60% but did not affect that induced by VE. Plasma OT concentration was significantly increased from 10.2 +/- 1.7 to 18.8 +/- 1.8 pg/ml at the end of HNa stimulation. In conclusion, the natriuresis in response to the intravenous sodium load was much more pronounced when NaCl was administered as a hypertonic solution than as an infusion inducing isotonic VE. Direct evidence was produced to assert that endogenous OT and its receptors are highly involved in the natriuresis elicited by systemic hypernatremic stimulation.
Parabrachial nucleus lesions impair feeding response elicited by 2,5-anhydro-D-mannitol
Authors: Grill H. J. , Friedman M. I. , Norgren R. , Scalera G. , Seeley R.
Published: December 2017

Systemic injection of the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) elicits a feeding response and induces c-fos activity in the parabrachial nuclei (PBN). We used bilateral ibotenic acid lesions of PBN to determine whether the activation inferred from c-fos activity was causally related to the feeding response. The relationship between the PBN lesion and feeding behavior was also examined with the glucose analogue 2-deoxy-D-glucose (2-DG). The PBN lesions interfered with the feeding response to 2,5-AM but spared the feeding response to 2-DG. Rats were also tested in a conditioned taste-aversion paradigm. Differences were observed in the relationship between lesion extent and behavioral deficit for feeding responses to 2,5-AM and taste-guided intake after taste-aversion conditioning. These data provide the first demonstration that central lesions can disrupt feeding responses to peripherally acting 2,5-AM. The results suggest that the neural substrate for this response differs from that mediating taste-aversion conditioning and from that involved in the feeding response to 2-DG.
Gestational effects on volume-sensitive cardiopulmonary receptor reflexes in the rat
Authors: Hines T. , Mifflin S. W.
Published: December 2017

We tested the hypothesis that augmented reflex sympathoinhibition mediated by volume-sensitive cardiopulmonary (CP) receptors contributes to the vasodilation of pregnancy by comparing responses to acute volume expansion in 21-day-pregnant and age-matched virgin rats (n = 7) that were anesthetized (pentobarbital sodium, 50 mg/kg ip), paralyzed (gallamine triethiodide, 25 mg/kg iv), ventilated, and had undergone bilateral sinoaortic denervation. CP receptors were stimulated with intra-atrial injections of saline (50, 100, 200, and 300 microliter), and the following variables were recorded: 1) mean right atrial pressure (MRAP) to index the afferent stimulus intensity; 2) cell discharge in the nucleus tractus solitarii (NTS), the primary central terminus for CP afferents; and 3) mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to assess efferent reflex effects. Basal MAP was significantly lower in pregnant (71.5 +/- 3.8 mmHg) than in virgin rats (86.6 +/- 3.1 mmHg), and plasma volume was expanded in the pregnant group (17.6 +/- 1.1 vs. 10.0 +/- 0.7 ml, P < 0.05). Baseline MRAP was similar between groups. Saline injections evoked graded increases in MRAP, which were larger in gravid animals (P < 0.05). Volume injections evoked similar changes in NTS cell discharge between groups, but the responses were nongraded. Despite larger changes in MRAP in gravid rats, reflex effects on RSNA and HR were similar to those in control animals, and effects on MAP were attenuated in the pregnant group. We conclude that larger changes in MRAP in pregnant rats during stimulation of CP receptors are not associated with larger changes in central or efferent components of this reflex.(ABSTRACT TRUNCATED AT 250 WORDS)
Responses of the branchial circulation to hypoxia in the Atlantic cod, Gadus morhua
Authors: Sundin L. I.
Published: December 2017

Simultaneous measurements of ventral aortic pressure, dorsal aortic pressure, cardiac output, and branchial venous flow were made to assess the effects of external hypoxia on the branchial vasculature in vivo. In addition, the effects of exogenously added amines (epinephrine and serotonin) and their antagonists (prazosin, sotalol, and methysergide) were assessed. The net effect of hypoxia was to increase branchial venous flow. Mechanisms involved in the branchial vasomotor control include an alpha-adrenoceptor-mediated vasoconstriction, as well as a nonadrenergic, possibly serotonergic, vasodilation of the arteriovenous pathway. The arterioarterial vascular resistance remained largely constant during hypoxia: a beta-adrenoceptor vasodilator effect was offset by vasoconstrictor factors that could be unmasked by sotalol treatment. One of these arterioarterial vasoconstrictors may be serotonin (released from serotonergic nerves or neuroepithelial cells), acting on the efferent filamental artery sphincters. The vascular adjustments during hypoxia increased the portion of cardiac output that flowed to the arteriovenous pathway. This may be of importance in providing the heart and the ion-regulatory cells of the filamental epithelium with oxygenated blood.
In vivo diuretic actions of renal vasopressin V1 receptor stimulation in rats
Authors: Ledderhos C. , Mattson D. L. , Skelton M. M. , Cowley A. W.
Published: December 2017

The specific vasopressin V1 receptor agonist (V1AG; [Phe2,Ile3,Orn8]vasopressin) was infused (2.0 ng.kg-1.min-1) into the renal medullary interstitial space to determine the effects of selective medullary V1 receptor stimulation on sodium and water excretion in normal rats. Responses were compared with those of arginine vasopressin (AVP) and vasopressin V2 receptor stimulation resulting from infusion of a V1 receptor antagonist with AVP. Medullary infusion of V1AG or AVP in euvolemic rats produced no changes in hemodynamics or glomerular filtration rate. V1AG increased urine flow > 60% in euvolemic rats, whereas no change was observed with AVP. This response could not be explained by a rise of arterial pressure or by volume retention. With V2 stimulation in euvolemic rats, urine flow was decreased. In water diuretic rats, V1AG produced no change, whereas AVP infusion decreased urine flow. The results provide in vivo evidence that tubular V1 vasopressin receptor activity results in increased urine flow and thereby modulates the antidiuretic actions of vasopressin in the euvolemic state.
Osmotic stimulation of vasopressin mRNA content in the supraoptic nucleus requires synaptic activation
Authors: Sladek C. D. , Fisher K. Y. , Sidorowicz H. E. , Mathiasen J. R.
Published: December 2017

The role of synaptic input to the vasopressin neurons in hypertonicity-induced increase in vasopressin mRNA content was evaluated. Synaptic connection with the anterior hypothalamus is required for hypertonicity to increase vasopressin release. However, the potential for other mechanisms to induce the increase in vasopressin mRNA content is suggested by the fact that hypertonicity induces depolarization of supraoptic neurons independently of synaptic input. Explants of the hypothalamoneurohypophysial system were used to study the effect of depolarization and hypertonicity in the presence and absence of nonspecific synaptic blockade by 15 mM MgSO4 or blockade of excitatory amino acid receptors with kynurenic acid. Vasopressin release and mRNA content were increased by depolarization with 40 mM KCl and by exposure to hypertonicity (P < 0.05). Basal and osmotically stimulated vasopressin release was decreased by MgSO4 and by kynurenic acid. Both agents prevented the hypertonicity-induced increase in vasopressin mRNA content. Thus either synaptic input or increased VP release is required for hypertonicity to increase vasopressin mRNA, and excitatory amino acids are implicated in this response.
Effect of L-alanine and ouabain on membrane conductances and apical membrane potential in Aplysia intestine
Authors: Gabbard S. R. , Moran W. M.
Published: December 2017

The proximal intestine of Aplysia californica was employed to assess the effect of alanine absorption on apical membrane K+ conductance (GKa) and basolateral membrane conductance (Gb) and the role of the electrogenic Na(+)-K(+)-adenosinetriphosphatase (Na+ pump) in the repolarization of apical membrane electrical potential difference (Va) after alanine-induced depolarization. Addition of 50 mM L-alanine (isosmotic substitution for mannitol) to the apical superfusate depolarized Va, reduced the ratio of apical to basolateral membrane resistances (Ra/Rb), and stimulated short-circuit current (Isc). Following these initial events, Va repolarized, Ra/Rb increased, and there was a slight decline in Isc. Apical high-K+ artificial seawater revealed an alanine-induced increase in GKa. Washout of alanine from the apical solution increased Ra/Rb above the prealanine control value. Thus alanine absorption is accompanied by an increase in Gb. Basolateral 0.1 mM ouabain abolished alanine-stimulated Isc but had little effect on Va ( < 3 mV depolarization) either before or after exposure to alanine. The repolarization of Va was not affected in tissues superfused with 0.1 mM basolateral ouabain for approximately 3 min even though the alanine-stimulated increase in Isc was abolished. Therefore, the electrogenic Na+ pump contributes minimally to the repolarization of Va in sea hare intestine. The origin of the hyperpolarization of Va resides therefore, at least in part, in the increase in GKa, which restores the driving force for Na(+)-alanine cotransport and prevents K+ accumulation in the enterocytes.
Intracellular pH in lizards after hypercapnia
Authors: Snyder G. K. , Nestler J. R. , Shapiro J. I. , Huntley J.
Published: December 2017

We used the transmembrane distribution of 5,5-[2-14C]dimethyloxazolidine-2,4-dione ([14C]DMO) and 31P magnetic resonance spectroscopy (NMR) to investigate the effects of hypercapnia on intracellular pH (pHi) in brain and skeletal muscle of two lizard species: Anolis equestris and Dipsosaurus dorsalis. In control animals (normocapnic), plasma PCO2 (3.3 +/- 0.1 kPa) and plasma pH (7.52 +/- 0.01) for D. dorsalis were not significantly different from the values for A. equestris (2.8 +/- 0.2 kPa and 7.59 +/- 0.02, respectively). Furthermore 60 min of 5% CO2 increased plasma PCO2 and decreased plasma pH by the same amounts in both species. Brain pHi values determined with the DMO method were not significantly different from values determined with NMR. Control values of brain pHi (DMO, 7.16 +/- 0.01; NMR, 7.11 +/- 0.02) and muscle pHi were significantly higher for D. dorsalis (DMO, 7.15 +/- 0.03) than for A. equestris (DMO, 6.99 +/- 0.03; NMR, 7.02 +/- 0.02 for brain; DMO, 6.97 +/- 0.03 for muscle). In addition, changes in tissue pHi after 60 min of 5% CO2 were significantly different for the two species. In D. dorsalis muscle and brain pHi decreased significantly after hypercapnia, whereas in A. equestris muscle pHi decreased significantly but brain pHi was unchanged. Our findings were independent of the methods used to determine pHi. The smaller change in brain and muscle pHi than in plasma pH for A. equestris is consistent with the view that pHi regulation involves active processes such as transmembrane ion transport.(ABSTRACT TRUNCATED AT 250 WORDS)
Central inspiration increases barosensitivity of neurons in rat rostral ventrolateral medulla
Authors: Miyawaki T. , Pilowsky P. , Sun Q. J. , Minson J. , Suzuki S. , Arnolda L. , Llewellyn-Smith I. , Chalmers J.
Published: December 2017

Barosensitive neurons in the rostral ventrolateral medulla (RVLM) often have a respiratory-related modulation of their activity. However, the extent of the interaction between baroreceptor and respiratory inputs is controversial. The main aim of the present study was to determine the effect of central respiratory drive (CRD) on the barosensitivity of RVLM neurons. Extracellular recordings were obtained from 68 barosensitive neurons in the RVLM of anesthetized, paralyzed, and bilaterally vagotomized Sprague-Dawley rats. Examination of phrenic-triggered histograms revealed five activity patterns among barosensitive neurons: inspiratory depression (type I, n = 20), early inspiratory activation (type II, n = 14), postinspiratory activation (type III, n = 18), expiratory depression (type IV, n = 5) and no modulation (type V, n = 11). In most neurons (types I and III and 56% of type II) inhibition produced by aortic nerve stimulation was greater in inspiration than in expiration. Cardiac-related modulation, as an index of natural phasic baroreceptor activation, was also greater in inspiration than expiration in type III neurons. The results demonstrate that CRD modulates the baroreflex at the level of the RVLM.
Light-induced suppression of the rat circadian system
Authors: Depres-Brummer P. , Levi F. , Metzger G. , Touitou Y.
Published: December 2017

In a constant environment, circadian rhythms persist with slightly altered period lengths. Results of studies with continuous light exposure are less clear, because of short exposure durations and single-variable monitoring. This study sought to characterize properties of the oscillator(s) controlling the rat's circadian system by monitoring both body temperature and locomotor activity. We observed that prolonged exposure of male Sprague-Dawley rats to continuous light (LL) systematically induced complete suppression of body temperature and locomotor activity circadian rhythms and their replacement by ultradian rhythms. This was preceded by a transient loss of coupling between both functions. Continuous darkness (DD) restored circadian synchronization of temperature and activity circadian rhythms within 1 wk. The absence of circadian rhythms in LL coincided with a mean sixfold decrease in plasma melatonin and a marked dampening but no abolition of its circadian rhythmicity. Restoration of temperature and activity circadian rhythms in DD was associated with normalization of melatonin rhythm. These results demonstrated a transient internal desynchronization of two simultaneously monitored functions in the rat and suggested the existence of two or more circadian oscillators. Such a hypothesis was further strengthened by the observation of a circadian rhythm in melatonin, despite complete suppression of body temperature and locomotor activity rhythms. This rat model should be useful for investigating the physiology of the circadian timing system as well as to identify agents and schedules having specific pharmacological actions on this system.
Metabolism of erythropoietin in conscious pregnant rats
Authors: Gough S. R. , Mosher M. D. , Conrad K. P.
Published: December 2017

Circulating erythropoietin (EPO) concentration increases during human and rat gestation, thereby contributing to the expansion of red cell mass. However, the mechanism(s) underlying gestational increases of the hormone is unknown. Our objective was to define whether the elevated EPO levels are secondary to decreased metabolic clearance or to enhanced production. The half-life of the hormone was also measured. A bolus and a constant infusion of 125I-labeled recombinant human EPO (125I-rhEPO) were administered to chronically instrumented conscious pregnant and virgin rats. The metabolic clearance rate of the 125I-rhEPO was slightly but significantly higher in gravid rats than in the virgin control animals (0.13 +/- 0.01 vs. 0.10 +/- 0.01 ml/min). The plasma half-life of 125I-rhEPO was 2.9 +/- 0.1 h for the pregnant rats and 2.9 +/- 0.2 h for the virgin controls. To confirm these results obtained by using 125I-rhEPO, EPO-rich plasma was generated in anemic rats and administered to another group of conscious virgin and pregnant rats. The half-life of homologous EPO was 2.9 +/- 0.5 and 3.3 +/- 0.1 h for gravid and virgin rats, respectively (P = NS). We conclude that elevated circulating EPO in rat gestation is secondary to increased biosynthesis and not to decreased metabolic clearance.
Mechanical basis of ANP secretion in beating atria: atrial stroke volume and ECF translocation
Authors: Cho K. W. , Kim S. H. , Kim C. H. , Seul K. H.
Published: December 2017

To investigate the mechanism by which an increase in pacing frequency or distension increases the secretion of atrial natriuretic peptide (ANP), the changes in atrial volume during contraction (atrial stroke volume), transmural transport of the extracellular fluid (ECF), and ANP secretion were quantified in the beating perfused rabbit atria. The atrium was stimulated by transmural field stimulation or by atrial distension induced by an increase in intraatrial pressure. Atrial stretch and incremental increases in pacing frequency up to 2 Hz activated the secretion of ANP coincident with an increase in atrial stroke volume and the transendocardial translocation of the ECF. These results showed positive relationships between changes in the secretion of ANP and the atrial stroke volume or the translocation of the ECF. The translocation of the ECF was also positively correlated with the change in atrial stroke volume. The accentuated secretion of ANP and translocation of the ECF waned at higher stimulating rates to show a peak value. Even under this condition, the secretion of ANP was a function of the translocation of the ECF. These data suggest that the increases in atrial stroke volume and translocation of ECF are fundamental factors in the ANP stimulation in response to atrial stretch and increases in atrial rate.