bluuebunny/crossref_metadata_2025 huggingface dataset:
Carotid baroreflex control of heart rate during acute exposure to simulated altitudes of 3,800 m and 4,300 m
Authors: Sagawa S. , Torii R. , Nagaya K. , Wada F. , Endo Y. , Shiraki K.
Published: December 2017

To examine the baroreflex response in humans during acute high-altitude exposure, the carotid baroreflex cardiac responsiveness was studied using a neck chamber in seven unacclimatized male subjects. Measurements were made in a high-altitude chamber on separate days at sea level and during 1-h exposure at two different altitudes of 3,800 m [partial pressure of oxygen in inspired air (Pi O2 ) = 90 mmHg] and 4,300 m (Pi O2  = 82 mmHg). R-R intervals were plotted against neck chamber pressures, and the baroreceptor response was analyzed by applying a four-parameter sigmoidal logistic function. The baroreceptor response curve shifted downward in either altitude, reflecting a tachycardic response at high altitude, and the magnitude of the shift was greater at 4,300 m than at 3,800 m. There was no change in the sigmoidal parameters at 3,800 m compared with sea level except for a reduction ( P < 0.05) of the minimum R-R interval. At 4,300 m the maximal R-R range, slope coefficient, minimum R-R interval, and maximal gain of the curve decreased significantly ( P < 0.05) compared with sea level values, whereas the centering point of the curve remained unchanged. These results suggest that hypoxia (Pi O2  = 82 mmHg) reduces the sensitivity of carotid baroreflex cardiac response.
Dietary NaCl and KCl do not regulate renal density of the thiazide diuretic receptor
Authors: Fanestil Darrell D. , Vaughn Duke A. , Blakely Patricia
Published: December 2017

We tested the postulate that the renal density of the thiazide-inhibitable Na-Cl cotransporter or thiazide receptor (TZR) is modulated as part of the renal homeostatic response to changes in dietary intake of NaCl or KCl. Renal excretion of NaCl or KCl varied >10-fold in response to alterations in oral intake. Renal TZR density was quantitated by binding of [3H]metolazone to renal membranes. Renal TZR density was not altered by sodium deficit (with increased plasma aldosterone concentration), by sodium surfeit (8% NaCl content of diet), by potassium deficit (with hypokalemia), or by potassium surfeit (drinking 1% KCl solution). Unexpectedly, we conclude that regulation of the renal density of TZR is not part of the renal homeostatic responses that adjust excretion of NaCl and KCl to changes in dietary intake of NaCl or KCl.
Aging alters feed-forward and feedback linkages between LH and testosterone in healthy men
Authors: Mulligan Thomas , Iranmanesh Ali , Johnson Michael L. , Straume Martin , Veldhuis Johannes D.
Published: December 2017

To discern the effect of aging on coordinate luteinizing hormone (LH) and testosterone secretion, we sampled healthy older men (age 62–74 yr, n = 11) and young controls (age 21–34 yr, n = 13) every 2.5 min overnight. Deconvolution analysis and cross-correlation were used to relate serum LH concentrations to calculated testosterone secretion rates (feed-forward stimulation), as well as serum testosterone concentrations to computed LH secretion rates (feedback inhibition). Despite statistically similar mean serum LH and testosterone concentrations in the young and older men, older individuals had diminished feed-forward stimulation of LH concentrations on calculated testosterone secretion rates, as well as delayed feedback inhibition of testosterone concentrations on computed LH secretion rates.
Aging and fluid homeostasis in rats
Authors: Rowland Neil E. , Morien Annie , Garcea Mircea , Fregly Melvin J.
Published: December 2017

The capacity of aging rats to defend body fluid homeostasis in response to a variety of dipsogenic and natriorexigenic stimuli was assessed. Male and female rats of both the Fischer 344 (FR) and Sprague-Dawley (SD) strains were used and tested at target ages of ∼5, 10, 15, and 20 mo in both longitudinal and cross-sectional studies. There were no consistent age-related declines in water intake in response to water deprivation or acute administration of hypertonic NaCl; angiotensin (ANG) I, II, III; or isoproterenol. Likewise, there were no major impairments in either urinary excretion of the hypertonic NaCl load or excretion of water or hypotonic NaCl loads, although the latter were excreted more slowly in the older cohorts. The preference/aversion functions for NaCl solutions differed between SD and FR rats, but did not change with age except in male FR rats that lost their aversion to dilute NaCl at 20 mo of age. Intake of hypotonic NaCl solution after acute sodium depletion (furosemide treatment) showed a partial decline with age, and the older rats sustained larger estimated sodium deficits after a 6-h repletion period. A more complete age-related decline was observed in the intake of hypertonic NaCl stimulated by chronic dietary administration of a kininase II inhibitor (ramipril). Male rats of 15–20 mo of age showed no ramipril-induced sodium appetite. Brain ANG II receptor density, determined by autoradiography, declined by almost 50% in the paraventricular nucleus at 20 mo of age and declined slightly in the organum vasculosum laminae terminalis but did not decline in either the supraoptic nucleus or subfornical organ. Thus the major deficits in fluid intake in aging rats are related to salt appetite; the mechanism was not identified definitively.
Use of feces to estimate isotopic abundance in doubly labeled water studies in reindeer in summer and winter
Authors: Gotaas Geir , Milne Eric , Haggarty Paul , Tyler Nicholas J. C.
Published: December 2017

The reliance on samples of blood or urine to estimate isotopic abundance in studies of energy metabolism using the doubly labeled water method has restricted application of the technique to animals that are either tame or easy to catch. This is generally not the case with large, free-ranging wild mammals. The use of feces as a source of body water in which to measure the concentration of isotopic markers was investigated in four female reindeer in summer and in winter.2H2O and H2 18O were injected to ∼160 parts per million excess. Samples of plasma and feces were then collected simultaneously for up to 456 h. Both isotopes were equilibrated with body water at 8 h postdose. There were no significant differences by animal between dilution spaces, rate constants, rates of CO2production, and total energy expenditure (TEE) calculated based on samples of plasma or feces in any trial. Mean TEE was 3.557 W/kg (SD 0.907, n = 4) in summer and 1.865 W/kg (SD 0.166, n = 4) in winter.
Renal and vascular effects of C-type and atrial natriuretic peptides in humans
Authors: Pham Isabelle , Sediame Saïd , Maistre Geneviève , Roudot-Thoraval Françoise , Chabrier Pierre-Etienne , Carayon Alain , Adnot Serge
Published: December 2017

C-type natriuretic peptide (CNP) may affect renal and vascular functions differently from atrial natriuretic peptide (ANP). The objective of this study was to compare the renal and vascular actions of CNP to those of ANP in normal men. CNP or ANP (0.005, 0.01, and 0.05 μg ⋅ kg−1⋅ min−1) were given by infusion to eight healthy volunteers. CNP caused dose-dependent increases in natriuresis (UNa) and in the fractional excretion of sodium (FENa) with no effect on diuresis (UV), renal plasma flow, and glomerular filtration rate (GFR). Fraction of filtration (FF) increased only with the 0.05 μg ⋅ kg−1⋅ min−1CNP dose. ANP caused larger increases in UNa, FENa, and FF than CNP and also increased UV at 0.01 and 0.05 μg ⋅ kg−1⋅ min−1and GFR at 0.05 μg ⋅ kg−1⋅ min−1. Although the ANP and CNP infusions produced similar elevation in the respective peptides plasma levels, urinary and nephrogenous guanosine 3′,5′-cyclic monophosphate increased less in response to CNP than to ANP. Blood pressure, forearm blood flow, plasma renin activity, and aldosterone remained unaffected during the peptides infusion. Plasma ANP increased slightly during CNP infusion. Our data indicate a higher threshold of renal response to CNP than to ANP. In contrast to ANP, CNP probably may not act as an endocrine factor in humans.
Fat accretion and the regulation of insulin-mediated glycogen synthesis after puberty in rats
Authors: Banerjee Swati , Saenger Paul , Hu Meizhu , Chen Wei , Barzilai Nir
Published: December 2017

Peripheral insulin sensitivity decreases after puberty in both humans and rodents and can be explained mostly by a reduction in insulin-mediated glycogen synthesis. We tested the hypothesis that the increase in postpubertal fat mass (FM), reflecting an alternative energy store, regulates a decrease in the capacity to store muscle glycogen. We studied Sprague-Dawley rats ( n = 21) before puberty (Pre) or after puberty (at 4 mo of age) in groups that were either ad libitum fed (Post) or moderately caloric restricted (CR). FM (by3H2O isotope dilution technique) was decreased by >40% in CR compared with Post. Glucose uptake (Rd, by 18 mU ⋅ kg−1⋅ min−1hyperinsulinemic clamp) was 63 ± 8 mg ⋅ kg−1⋅ min−1in Pre and decreased to 39 ± 2 mg ⋅ kg−1⋅ min−1in Post ( P < 0.001). However, it increased in CR to 53 ± 2 mg ⋅ kg−1⋅ min−1( P < 0.001 vs. Post). This increase in Rdwas mainly accounted for by an increase in glycogen synthesis (Rdglycolysis determined by the rate of conversion of3H-labeled glucose to3H2O) from 23 ± 2 in Post to 33 ± 2 mg ⋅ kg−1⋅ min−1in CR ( P < 0.001; 38 ± 7 mg ⋅ kg−1⋅ min−1in Pre). Correction of glycogen synthesis in CR to near-prepubertal levels was further supported by directly assayed muscle glycogen content after insulin stimulation that was 45% higher and by a 35% enhanced accumulation of [3H]glucose into glycogen. No changes in the enzyme kinetics of glycogen synthase or phosphorylase were observed. An additional group of 2-mo-old postpubertal ad libitum-fed rats was matched with CR for lean body mass but had more FM. This group demonstrated 25% lower rates of insulin-mediated glycogen synthesis compared with CR, further supporting the notion that a moderate reduction of FM prevents the decline in insulin responsiveness and glycogen synthesis occurring after puberty. These data suggest a cause-effect relationship between the increased deposition of fat and the reduced ability to store glucose in skeletal muscle after puberty.
Is the hypotensive effect of clonidine and related drugs due to imidazoline binding sites?
Authors: Guyenet Patrice G.
Published: December 2017

Clonidine and related α2-adrenergic receptor (α2AR) agonists lower arterial pressure primarily by an action within the central nervous system. These drugs also have varying degrees of affinity for other cellular components called nonadrenergic imidazoline binding sites (NAIBS). For over 20 years, the α2AR agonist activity of clonidine-like drugs was thought to account for their therapeutic effects (α2 theory). However, several groups have recently proposed a competing “imidazoline theory” according to which the hypotensive effect of clonidine-like drugs would in fact owe more to their affinity for one type of NAIBS, called I1receptors. The α2-theory is strongly supported by four main types of congruent data. First, the hypotensive effect of systemically administered clonidine is blocked by α2AR antagonists that are without affinity for I1 NAIBs. Second, the hypotensive effect of intravenous clonidine is absent in genetically engineered mice in which a defective α2AAR has been substituted for the normal one. Third, the sympatholytic effect of clonidine is consistent with the presence of conventional inhibitory α2ARs on sympathetic preganglionic neurons and on their main excitatory inputs in the medulla oblongata. Fourth, the first I1 ligand without affinity for α2ARs was found to be biologically inactive. The imidazoline theory is supported by a limited repertoire of whole animal “in vivo” pharmacological experiments that remain open to a wide range of interpretations. In conclusion, the bulk of the evidence strongly supports a largely predominant role of α2AR mechanisms in the action of most clonidine-like agents at therapeutically relevant doses or concentrations. Even the small pharmacological differences between these agents cannot yet be linked with certainty to their relative affinity for I1 NAIBS.
Glycyl-l-glutamine [β-endorphin-(30—31)] attenuates hemorrhagic hypotension in conscious rats
Authors: Owen Medge D. , Gürün Sibel , Zaloga Gary P. , Millington William R.
Published: December 2017

The profound hypotension caused by acute hemorrhage is thought to involve opioid peptide neurons. In this study, we tested whether glycyl-l-glutamine [Gly-Gln; β-endorphin-(30—31)], a nonopioid peptide derived from β-endorphin processing, prevents the cardiovascular depression induced by hemorrhage in conscious and anesthetized rats. Previously, we found that Gly-Gln inhibits the hypotension and respiratory depression produced by β-endorphin and morphine but does not affect opioid antinociception. Hemorrhage (2.5 ml/100 g body wt over 20 min) lowered arterial pressure in conscious rats (from 120.1 ± 2.9 to 56.2 ± 4.7 mmHg) but did not change heart rate significantly. Intracerebroventricular Gly-Gln (3, 10, or 30 nmol) pretreatment inhibited the fall in arterial pressure and increased heart rate significantly. The response was dose related and was sustained during the 35-min posthemorrhage interval. Pentobarbital sodium anesthesia potentiated the hemodynamic response to hemorrhage and attenuated the effect of Gly-Gln. Gly-Gln (10 or 100 nmol icv) did not influence arterial pressure or heart rate in normotensive rats. These data indicate that Gly-Gln is an effective antagonist of hemorrhagic hypotension.
5-CT or DOI augments TRH analog-induced gastric acid secretion at the dorsal vagal complex
Authors: Varanasi Sridhar , Chi Jinhan , Stephens Robert L.
Published: December 2017

Serotonin (5-HT) interacts with thyrotropin-releasing hormone (TRH) at the dorsal vagal complex (DVC) to augment TRH-induced stimulation of gastric acid secretion. To investigate the 5-HT receptor family involved in the augmentation response, prototypical 5-HT receptor-selective agonists (146 pmol) were coinjected with the TRH analog RX-77368 (RX; 12 pmol) into the rat DVC in a 30-nl volume. The DVC coordinates were 0.2 mm anterior, 0.2 mm right, 0.6 mm ventral with respect to the calamus scriptorius. Coinjection of RX with the 5-HT agonists 5-carboxyamidotryptamine (5-CT) or (±)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI; 5-HT2 agonist) produced a 183 or 103% increase in gastric acid output compared with the RX injection alone. In contrast, coinjection of 2- methyl-5-HT (5-HT3 agonist) with RX produced no effect on RX-induced increase in gastric acid secretion. Moreover, coinjection of SC-53116 (5-HT4agonist) decreased the gastric acid output by 45% compared with the RX response itself. Examination of the RX/5-HT agonist coinjection response in more rostral regions of the DVC using the same doses (5-CT/RX or DOI/RX) revealed that only 5-CT was effective in producing the augmented response to TRH analog. The results suggest that activation of 5-CT- or DOI-sensitive receptors augments, and of 5-HT4 receptors inhibits, the gastric acid response to TRH analog injected into the DVC. Thus the integrated response to several serotonin receptor subtypes may mediate changes to the TRH response induced by 5-HT at the DVC.
DHEA protects against visceral obesity and muscle insulin resistance in rats fed a high-fat diet
Authors: Hansen Polly A. , Han Dong Ho , Nolte Lorraine A. , Chen May , Holloszy John O.
Published: December 2017

Visceral obesity is frequently associated with muscle insulin resistance. Rats fed a high-fat diet rapidly develop obesity and insulin resistance. Dehydroepiandrosterone (DHEA) has been reported to protect against the development of obesity. This study tested the hypothesis that DHEA protects against the increase in visceral fat and the development of muscle insulin resistance induced by a high-fat diet in rats. Feeding rats a diet providing 50% of the energy as fat for 4 wk resulted in a twofold greater visceral fat mass and a 50% lower rate of maximally insulin-stimulated muscle 2-deoxyglucose (2-DG) uptake compared with controls. Rats fed the high-fat diet plus 0.3% DHEA were largely protected against the increase in visceral fat (+11.3 g in high fat vs. +2.9 g in high fat plus DHEA, compared with controls) and against the decrease in insulin-stimulated muscle 2-DG uptake (0.94 ± 0.15 μmol ⋅ ml−1⋅ 20 min−1, controls; 0.46 ± 0.06 μmol ⋅ ml−1⋅ 20 min−1, high-fat diet; 0.78 ± 0.07 μmol ⋅ ml−1⋅ 20 min−1, high fat + DHEA). DHEA did not affect food intake. These results show that DHEA has a protective effect against accumulation of visceral fat and development of muscle insulin resistance in rats fed a high-fat diet.
pH-dependent proton secretion in cultured swim bladder gas gland cells
Authors: Pelster B. , Niederstätter H.
Published: December 2017

The pH dependence of acid production and of acid release has been analyzed in cultured gas gland cells of the European eel using a cytosensor microphysiometer. Total acid release of gas gland cells showed an optimum at pH 7.4–7.6, with only a minor reduction at acidic (pH 7.0) as well as at alkaline pH (pH 8.0). The acid production was largely dependent on the availability of extracellular glucose and was almost completely abolished if glucose was replaced by succinate, alanine, or even pyruvate. Phloretin, an inhibitor of glucose uptake, significantly reduced acid release of gas gland cells with a Kiof ∼1 × 10−5M, irrespective of pH. Although the glucose dependence of acid production was not modified by pH, acid release became increasingly sodium dependent with decreasing pH, but at low pH significantly higher sodium concentrations were necessary to achieve maximal rate of proton secretion. This sodium-dependent proton secretion could only in part be inhibited by application of 5-( N-methyl- N-isobutyl)-amiloride. Removal of extracellular potassium caused a slow reduction in the rate of acid secretion. A similar reduction was observed in the presence of ouabain, a specific inhibitor of Na+-K+-adenosinetriphosphatase, and both effects significantly increased with decreasing pH. The results demonstrate a significant pH dependence of the mechanisms of acid release in swim bladder gas gland cells and indicate that sodium-dependent pathways become especially important at low pH.
Effect of chronic hypoxia on glucose transporters in heart and skeletal muscle of immature and adult rats
Authors: Xia Ying , Warshaw Joseph B. , Haddad Gabriel G.
Published: December 2017

Glucose transporter (GLUT) modulation can be an important mechanism that contributes to adaptation to hypoxic stress, but little is known about GLUT modulation in heart and skeletal muscle with prolonged hypoxia. In this work, the effect of chronic hypoxia on GLUT-4 and GLUT-1 mRNA and protein was studied in these two tissues in the adult and during development. Hypoxia (fractional inspired O2= 9 ± 0.5%) was administered to two groups, i.e., an immature group exposed from 3 to 30 days of age and an adult group exposed from 90 to 120 days of age. Rats were then killed and their heart and skeletal muscles were sampled for measurements of GLUT mRNA and protein with Northern and Western blots. In the adult, chronic hypoxia significantly decreased cardiac GLUT mRNA level by >25% of control ( P < 0.05), but had little effect on GLUT protein. A very different hypoxic effect was seen in the immature rat heart with a major increase in protein and no appreciable change in mRNA density. Adult skeletal muscle had no change in GLUT mRNA level but GLUT protein increased (15–20%, P < 0.05) while both GLUT mRNA and protein were significantly increased in the immature skeletal muscles (60–90% over control). We conclude that during chronic O2deprivation, GLUT-1 and GLUT-4 expressions show a similar pattern but greatly depend on tissue type and age. These differences in GLUT regulation may be due to different strategies for coping with prolonged O2deprivation in both immature and adult animals.
Protection against glutamate-induced cytotoxicity in C6 glial cells by thiol antioxidants
Authors: Han Derick , Sen Chandan K. , Roy Sashwati , Kobayashi Michael S. , Tritschler Hans J. , Packer Lester
Published: December 2017

In many cell lines, glutamate cytotoxicity is known to be mediated by an inhibition of cystine transport. Because glutamate and cystine share the same transporter, elevated levels of extracellular glutamate competitively inhibit cystine transport leading to depletion of intracellular glutathione. A glutathione-depleted state impairs cellular antioxidant defenses resulting in oxidative stress. It was therefore of interest to investigate whether proglutathione agents, e.g., N-acetylcysteine and lipoic acid, are able to protect against glutamate cytotoxicity. Both lipoic acid (100 μM-1 mM) and N-acetylcysteine (100 μM-1 mM) completely protected C6 cells from the glutamate-induced cell death. Both agents facilitate extracellular supply of cysteine, the reduced form of cystine, that is transported into the cell by a glutamate-insensitive transport mechanism. Protection by lipoic acid and N-acetylcysteine corresponded with a sparing effect on cellular glutathione, which is usually depleted after glutamate treatment. In the presence ofl-buthionine-( S, R)-sulfoximine, a γ-glutamylcysteine synthetase inhibitor, low doses (<100 μM) of lipoic acid and N-acetylcysteine did not protect cells against glutamate-induced cytotoxicity. At higher concentrations (>500 μM), however, both lipoic acid and N-acetylcysteine provided partial protection against glutamate cytotoxicity even in glutathione synthesis-arrested cells. These results indicate that at low concentrations the primary mechanism of protection by the thiol antioxidants was mediated by their proglutathione property rather than direct scavenging of reactive oxygen. At higher concentrations (>500 μM), a GSH-independent direct antioxidant effect of lipoic acid and N-acetylcysteine was observed. Dichlorofluorescin fluorescence, a measure of intracellular peroxides, increased sixfold after glutamate treatment of C6 cells. Lipoic acid and N-acetylcysteine treatment significantly lowered glutamate-induced dichlorofluorescin fluorescence compared with that of controls. Interestingly, α-tocopherol (50 μM) also suppressed glutamate-induced dichlorofluorescin fluorescence, indicating the peroxides detected by dichlorofluorescin were likely lipid hydroperoxides. Both thiol antioxidants, particularly lipoic acid, appear to have remarkable therapeutic potential in protecting against neurological injuries involving glutamate and oxidative stress.
Developmental regulation of erythropoietin and erythropoiesis
Authors: Moritz K. M. , Lim Gaik Bee , Wintour E. M.
Published: December 2017

It is well established that erythropoiesis occurs first in the yolk sac, then in the liver, subsequently moving to the bone marrow and, in rodents, the spleen during development. The origin of the erythropoietic precursors and some factors suggested to be important for the changing location of erythropoiesis are discussed in this review. Until recently, the major site of erythropoietin (Epo) production in the fetus was thought to be the liver, but studies have shown now that the Epo gene is expressed strongly in the fetal kidney, even in the temporary mesonephros. The metanephric Epo mRNA is upregulated by anemia, downregulated by glucocorticoids, and contributes substantially to circulating hormone levels in hemorrhaged ovine fetuses. Other sites of Epo and Epo receptor production, likely to have important actions during development, are the placenta and the brain.
Systemic hemodynamic responses to chronic angiotensin II infusion into the renal artery of dogs
Authors: Fitzgerald Sharyn M. , Stevenson Kathleen M. , Evans Roger G. , Anderson Warwick P.
Published: December 2017

Chronic intrarenal infusion of angiotensin II (0.5 ng ⋅ kg−1⋅ min−1) in dogs increases arterial pressure. In the present study we determined whether this was associated with changes in cardiac output or in total peripheral resistance. Mean arterial pressure did not change initially but was significantly increased over days 14- 28 of the infusion period (+6 ± 2 mmHg), as was total peripheral resistance (+4 ± 2 mmHg ⋅ min ⋅ l−1). Neither cardiac output, renal blood flow, nor glomerular filtration rate was significantly changed over this period. To determine the influence of the autonomic nervous system on the developing hypertension, periodic acute autonomic ganglion blockade was performed. Before angiotensin II infusion ganglion blockade reduced total peripheral resistance and increased cardiac output, and this effect was similar across the 4 wk of angiotensin II infusion. Systemic hemodynamics were not affected by intravenous angiotensin II infusion (0.5 ng ⋅ kg−1⋅ min−1). Thus intrarenal infusion of low-dose angiotensin II produced a chronic increase in arterial pressure due to an action within the kidney. The hypertension was associated with increased total peripheral resistance but not with marked changes in cardiac output or renal function or in the influence of the autonomic nervous system on systemic hemodynamics.
Evidence that brief stress may induce the acute phase response in rats
Authors: Deak Terrence , Meriwether Jennifer L. , Fleshner Monika , Spencer Robert L. , Abouhamze Amer , Moldawer Lyle L. , Grahn Ruth E. , Watkins Linda R. , Maier Steven F.
Published: December 2017

Exposing rats to a single session of inescapable tail shock (IS) reduces corticosteroid binding globulin (CBG) 24 h later (Fleshner et al., Endocrinology 136: 5336–5342, 1995). The present experiments examined whether reductions in CBG are differentially affected by controllable vs. identical uncontrollable tail shock, are mediated by IS-induced glucocorticoid elevation, or reflect IS-induced activation of the acute phase response and whether IS produces fever. The results demonstrate that 1) equivalent reductions in CBG are observed in response to escapable tail shock or yoked IS, 2) IS-induced CBG reduction is not blocked by adrenalectomy in rats that receive basal corticosteroid replacement or by pretreatment with RU-38486, and 3) IS appears to activate the acute phase response, since IS reduces serum levels of an acute-phase negative reactant (CBG), increases serum levels of acute-phase positive reactants (haptoglobin and α1-acid glycoprotein), and increases core body temperature 20–24 h later.
Effects of hypoxia and low temperature on substrate fluxes in fish: plasma metabolite concentrations are misleading
Authors: Haman François , Zwingelstein Georges , Weber Jean-Michel
Published: December 2017

Oxygen levels and temperature can fluctuate rapidly in aquatic environments. Even though the effects of environmental stresses on fish metabolism have been studied extensively, information on fuel kinetics is extremely limited because it relies almost exclusively on changes in substrate concentrations. The turnover rate of nonesterified fatty acids (NEFA) has never been measured in fish. Therefore, our goal was to quantify glucose and NEFA fluxes in rainbow trout acutely exposed to severe hypoxia (25% O2saturation) or low temperature (6°C for fish acclimated to 15°C) by performing continuous infusions of 6-[3H]glucose and 1-[14C]palmitate in vivo. Results show that hypoxia causes a 53% decrease in NEFA turnover rate, together with a transient increase in hepatic glucose production, whereas a rapid drop in temperature induces equivalent declines in glucose, NEFA, and oxygen fluxes [temperature coefficient ≅ 2]. More importantly, kinetic changes in glucose and NEFA fluxes are not accompanied by interpretable changes in the plasma concentrations of these metabolites. Thus using concentration changes to draw conclusions about fluxes must be avoided.
GLUT-1 mediation of rapid glucose transport in dolphin (Tursiops truncatus) red blood cells
Authors: Craik James D. , Young James D. , Cheeseman Christoper I.
Published: December 2017

d-Glucose entry into erythrocytes from adult dolphins ( Tursiops truncatus) was rapid, showed saturation at high substrate concentrations, and demonstrated a marked stimulation by intracellular d-glucose. Kinetic parameters were estimated from the concentration dependence of initial rates of tracer entry at 6°C: for zero- trans entry, Michaelis constant ( Km) was 0.78 ± 0.10 mM and maximal velocity ( Vmax) was 300 ± 9 μmol ⋅ l cell water−1⋅ min−1; for equilibrium exchange entry, Kmwas 17.5 ± 0.6 mM and Vmaxwas 8,675 ± 96 μmol ⋅ l cell water−1⋅ min−1. Glucose entry was inhibited by cytochalasin B, and mass law analysis of reversible,d-glucose-displaceable, cytochalasin B binding gave values of 0.37 ± 0.03 nmol/mg membrane protein for maximal binding and 0.48 ± 0.10 μM for the dissociation constant. Dolphin glucose transporter polypeptides were identified on sodium-dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots [using antibodies that recognized human glucose transporter isoform (GLUT-1)] as two molecular species, apparent relative molecular weights of 53,000 and 47,000. Identity of these polypeptides was confirmed byd-glucose-sensitive photolabeling of membranes with [3H]cytochalasin B. Digestion of both dolphin and human red blood cell membranes with glycopeptidase F led to the generation of a sharp band of relative molecular weight 46,000 derived from GLUT-1. Trypsin treatment of human and dolphin erythrocyte membranes generated fragmentation patterns consistent with similar polypeptide structures for GLUT-1 in human and dolphin red blood cells.
Systemic inhibition of nitric oxide and prostaglandins in volume-induced natriuresis and hypertension
Authors: Krier James D. , Romero Juan Carlos
Published: December 2017

Nitric oxide (NO) synthesis inhibition with NG-nitro-l-arginine methyl ester (l-NAME) (10 μg ⋅ kg−1⋅ min−1iv), cyclooxygenase inhibition with meclofenamate (Meclo; 5 mg/kg iv bolus), and combination of drugs (l-NAME+Meclo) were used to investigate the roles of NO and prostaglandins (PG) in the hemodynamic and natriuretic responses to isotonic saline volume expansion (VE; 5% body wt over 60 min) in anesthetized dogs. Before VE,l-NAME ( n = 6), Meclo ( n = 6), andl-NAME+Meclo ( n = 6) produced significant increments in mean arterial pressure (MAP) of 12 ± 2, 15 ± 3, and 17 ± 3 mmHg, respectively. VE did not change MAP in Meclo-treated dogs, but produced a significant elevation in the control dogs (14 ± 6 mmHg), inl-NAME-treated dogs (17 ± 6 mmHg), and in dogs pretreated withl-NAME+Meclo (12 ± 5 mmHg). VE alone induced marked natriuretic responses in the control (38 ± 9 to 562 ± 86 μmol/min),l-NAME (31 ± 9 to 664 ± 65 μmol/min), and Meclo groups (41 ± 10 to 699 ± 51 μmol/min). However, this natriuretic response was attenuated in dogs pretreated with l-NAME+Meclo (12 ± 4 to 185 ± 52 μmol/min). These results indicate that 1) blockade of both NO and PGs has significant diminishing effects on volume-induced natriuresis, 2) NO blockade alone impairs volume-induced natriuresis in a manner that requires further increases in MAP to restore the natriuresis, and 3) PG blockade alone does not curtail volume-induced natriuresis.
Amiloride-induced contraction of isolated guinea pig, mouse, and human fetal airways
Authors: Christ Michael J. , Iwamoto Lynn M. , Silva Asoka de , Lavallee Sarah L. , Nakamura Kenneth T.
Published: December 2017

Nebulized amiloride has been proposed as therapy in cystic fibrosis to block Na+hyperabsorption in airway epithelium and prevent dehydration of secretions. Patients with cystic fibrosis often have reactive airways. Bovine and canine trachea relax to amiloride in vitro, suggesting another benefit as a bronchodilator, whereas guinea pig trachea, a useful model of human airways, does not. We hypothesized that human airways would respond like guinea pig airways. Airway ring segments from guinea pigs, mice, and human fetuses were constricted with the concentration of acetylcholine producing 50–75% maximum contraction. Subsequent changes in isometric tension to cumulative additions of amiloride (10−8–10−4M) were measured. Guinea pig airways contracted 29 ± 5%, mouse airways contracted 23 ± 6%, and human fetal airways contracted 30 ± 8%. Contraction to amiloride was mimicked by dimethylamiloride, a more selective inhibitor of the Na+/H+antiporter, and was attenuated by protein kinase C (PKC) inhibition with GF109203X and staurosporine. The present study indicates that amiloride-induced airway contraction in guinea pigs and mice closely parallels the response in isolated human airways and that the mechanism may involve the Na+/H+antiporter and PKC.
Torpor in lactating Siberian hamsters subjected to glucoprivation
Authors: Stamper Juliet L. , Zucker Irving , Lewis Daniel A. , Dark John
Published: December 2017

Daily torpor has never been reported for any rodent species during lactation. To test whether torpor and lactation are incompatible processes, we administered 2-deoxy-d-glucose (2-DG), a glucose analog that interferes with cellular glycolysis, to Siberian hamsters during the 2nd wk postpartum. 2-DG (2,500 mg/kg of body mass) induced torpor in lactating as well as nonlactating females. Although depth of torpor did not differ between groups, duration of torpor tended to be shorter in lactating animals. Evidence of new milk bands suggests that pups were able to obtain milk from torpid dams. By contrast, dams subjected either to a combination of brief food deprivation and subsequent food restriction or just food restriction failed to display torpor, but instead cannibalized one or more pups. We conclude that torpor is possible during lactation; whether lactating dams in nature become torpid in response to energy shortages or cannibalize or abandon one or more of their offspring remains unknown.
Dopamine D1receptor antagonist inhibits swallowing reflex in guinea pigs
Authors: Jia Yu Xia , Sekizawa Kiyohisa , Ohrui Takashi , Nakayama Katsutoshi , Sasaki Hidetada
Published: December 2017

To determine whether dopamine D1receptor antagonist impairs the swallowing reflex and reduces substance P (SP) in the peripheral organs, the swallowing reflex in terms of the number of swallows elicited by injections of three different volumes (0.2, 0.4, and 0.6 ml) of distilled water into the pharynx through a catheter was examined in anesthetized guinea pigs pretreated with Sch-23390. Animals were pretreated with either subcutaneous Sch-23390 (200 μg/kg) or a vehicle of Sch-23390 every 12 h for 7 days. The number of swallows was counted by submental electromyographic activity and visual observation of characteristic laryngeal movement. Injections of distilled water caused a volume-dependent increase in the number of swallows in animals without Sch-23390 treatment. Sch-23390 significantly decreased and exogenously administered SP increased the number of swallows elicited by all volumes of distilled water. FK-888 (10−5M, 1 ml), a specific inhibitor of the NK1receptor, reduced the number of swallows to a greater degree than Sch-23390. Sch-23390 significantly reduced SP content in the laryngeal and pharyngeal mucosa compared with control. These results suggest that inhibition of the dopamine D1receptor may impair the swallowing reflex and reduce SP content in the peripheral organs.
ACTH responses to hypotension and feedback inhibition of ACTH increased by chronic progesterone treatment
Authors: Keller-Wood Maureen
Published: December 2017

During pregnancy, arterial pressure, baroreceptor sensitivity, and adrenocorticotropic hormone (ACTH) responses to hypotension are decreased. Basal ACTH and cortisol are increased in pregnancy, suggesting a reduction in cortisol feedback inhibition of ACTH. Acute treatment with progesterone decreases arterial pressure, baroreflex-mediated responses, and corticosteroid feedback effects on ACTH. These experiments test the hypothesis that chronic increases in progesterone produce changes in arterial pressure, ACTH responses to stress, and feedback inhibition of ACTH similar to pregnancy. Ewes were treated with progesterone for 60–80 days. This increase in plasma progesterone (to 7.6 ± 0.4 ng/ml) did not alter basal ACTH, cortisol, arterial pressure, or heart rate. However, ACTH and AVP responses to hypotension were augmented in progesterone-treated ewes compared with untreated ewes. Chronic progesterone treatment resulted in greater inhibition of ACTH by cortisol. Because chronic progesterone treatment did not decrease the ACTH response to hypotension or attenuate the feedback control of ACTH secretion, these results suggest that the changes in pituitary-adrenal control during pregnancy do not reflect a simple effect of progesterone alone.
Juxtaglomerular cell complex in the regulation of renal salt excretion
Authors: Schnermann Jurgen
Published: December 2017

Luminal NaCl concentration at the macula densa (MD) has the two established effects of regulating glomerular arteriolar resistance and renin secretion. Tubuloglomerular feedback (TGF), the inverse relationship between MD NaCl concentration and glomerular filtration rate (GFR), stabilizes distal salt delivery and thereby NaCl excretion in response to random perturbations unrelated to changes in body salt balance. Control of vasomotor tone by TGF is exerted primarily by NaCl transport-dependent changes in local adenosine concentrations. During long-lasting perturbations of MD NaCl concentration, control of renin secretion becomes the dominant function of the MD. The potentially maladaptive effect of TGF under chronic conditions is prevented by TGF adaptations, permitting adjustments in GFR to occur. TGF adaptation is mechanistically coupled to the end point targeted by chronic deviations in MD NaCl, the rate of local and systemic angiotensin II generation. MD control of renin secretion is the result of the coordinated action of local mediators that include nitric oxide synthase (NOS) and cyclooxygenase (COX) products. Thus vascular smooth muscle cell activation during high MD transport and granular cell activation during low MD transport is achieved by different extracellular mediators. The coordinated regulation of NOS I and COX-2 expression in MD cells and of renin expression in granular cells suggests that control of juxtaglomerular regulation of gene transcription or mRNA metabolism may be another consequence of a chronic alteration in MD NaCl concentration.
Regulation of prostaglandin biosynthesis in vivo by glutathione
Authors: Margalit Alon , Hauser Scott D. , Zweifel Ben S. , Anderson Melissa A. , Isakson Peter C.
Published: December 2017

Intraperitoneal administration of urate crystals to mice reduced subsequent macrophage conversion of arachidonic acid (AA) to prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid for up to 6 h. In contrast, levels of 12-hydroxyheptadecatrienoic acid (12-HHT) were markedly elevated. This metabolic profile was previously observed in vitro when recombinant cyclooxygenase (COX) enzymes were incubated with reduced glutathione (GSH). Analysis of peritoneal GSH levels revealed a fivefold elevation after urate crystal administration. The GSH synthesis inhibitorl-buthionine-[ S, R]-sulfoximine partially reversed the urate crystal effect on both GSH elevation and PG synthesis. Moreover, addition of exogenous GSH to isolated peritoneal macrophages shifted AA metabolism from PGs to 12-HHT. Urate crystal administration reduced COX-1, but induced COX-2 expression in peritoneal cells. The reduction of COX-1 may contribute to the attenuation of PG synthesis after 1 and 2 h, but PG synthesis remained inhibited up to 6 h, when COX-2 levels were high. Overall, our results indicate that elevated GSH levels inhibit PG production in this model and provide in vivo evidence for the role of GSH in the regulation of PG biosynthesis.
Blood flow and glucose uptake in denervated, insulin-resistant muscles
Authors: Turinsky Jiri , Damrau-Abney Alice , Loegering Daniel J.
Published: December 2017

To investigate whether changes in blood flow contribute to the insulin resistance in denervated muscles, basal and insulin-stimulated 2-deoxy-d-glucose (2-DG) uptake in vivo and blood flow were measured in soleus (slow twitch), plantaris (fast twitch), and gastrocnemius (fast twitch) muscles at 1 and 3 days after a right hindlimb denervation in the rat. Muscles of the contralateral sham hindlimb served as an internal control. Sham plantaris and gastrocnemius muscles showed 32 and 60% lower basal 2-DG uptake, 46 and 66% lower insulin-stimulated 2-DG uptake, and 79 and 81% lower blood flow, respectively, compared with sham soleus muscle. At 1 day after denervation, soleus, plantaris, and gastrocnemius muscles exhibited an 80, 64, and 42% decrease in insulin-stimulated 2-DG uptake, respectively, in the presence of 63, 323, and 304% higher blood flow, respectively. At 3 days after denervation, soleus muscle showed a 60% decrease in basal 2-DG uptake, complete unresponsiveness to insulin, and an 86% decrease in blood flow. In contrast, the denervated plantaris and gastrocnemius muscles exhibited a 262 and 105% increase in basal 2-DG uptake, respectively, no change in insulin-stimulated 2-DG uptake, and no change in blood flow compared with corresponding contralateral sham muscles. The results demonstrate that muscle blood flow is influenced by muscle fiber population and time after denervation and that changes in blood flow do not contribute to the insulin resistance in the denervated muscles.
Time-dependent physiological regulation of rodent and ovine placental glucose transporter (GLUT-1) protein
Authors: Das Utpala G. , Sadiq H. Farouk , Soares Michael J. , Hay William W. , Devaskar Sherin U.
Published: December 2017

To examine the in vivo and in vitro time-dependent effects of glucose on placental glucose transporter (GLUT-1) protein levels, we employed Western blot analysis using placenta from the short-term streptozotocin-induced diabetic pregnancy (STZ-D), uterine artery ligation-intrauterine growth restriction (IUGR) rat models, pregnant sheep exposed to chronic maternal glucose and insulin infusions, and the HRP.1 rat trophoblastic cell line exposed to differing concentrations of glucose. In the rat, 6 days of STZ-D with maternal and fetal hyperglycemia caused no substantive change, whereas 72 h of IUGR with fetal hypoglycemia and ischemic hypoxia resulted in a 50% decline in placental GLUT-1 levels ( P < 0.05). In late-gestation ewes, maternal and fetal hyperglycemia caused an initial threefold increase at 48 h ( P< 0.05), with a persistent decline between 10 to 21 days, whereas maternal and fetal hypoglycemia led to a 30–50% decline in placental GLUT-1 levels ( P < 0.05). Studies in vitro demonstrated no effect of 0 mM, whereas 100 mM glucose caused a 60% decline ( P < 0.05; 48 h) in HRP.1 GLUT-1 levels compared with 5 mM of glucose. The added effect of hypoxia on 0 and 100 mM glucose concentrations appeared to increase GLUT-1 concentrations compared with normoxic cells ( P < 0.05; 100 mM at 18 h). We conclude that abnormal glucose concentrations alter rodent and ovine placental GLUT-1 levels in a time- and concentration-dependent manner; hypoxia may upregulate this effect. The changes in placental GLUT-1 concentrations may contribute toward the process of altered maternoplacentofetal transport of glucose, thereby regulating placental and fetal growth.
Vascular and hemodynamic effects of behavioral stress in borderline hypertensive and Wistar-Kyoto rats
Authors: Fuchs Leslie C. , Hoque Azizul M. , Clarke Natalie L.
Published: December 2017

In borderline hypertensive rats (BHR), behavioral stress produces hypertension, which has been attributed to increases in sympathetic nervous system activity and peripheral changes in vascular structure. However, the mechanisms mediating development of stress-induced hypertension have not been well defined. Experiments were designed to determine hemodynamic effects and changes in small mesenteric artery (≈300 μm) vascular reactivity in response to 10 days of air-jet stress (2 h/day) in BHR and in Wistar-Kyoto (WKY) rats. The acute stress-induced increase in mean arterial pressure (AP) was impaired in WKY rats compared with BHR on day 1, and habituation developed to the increase in AP in BHR, but not WKY rats. Conversely, WKY rats adapted to the stress-induced tachycardia to a larger extent than BHR. The mechanisms mediating endothelium-dependent relaxation to acetylcholine (ACh) were altered in small mesenteric arteries isolated from WKY rats and BHR after 10 days of air-jet stress. Inhibition of nitric oxide synthase activity had a significantly larger inhibitory effect on ACh-induced relaxation in vessels from stressed compared with control BHR. Also, cyclooxygenase products contributed to ACh-induced relaxation of small mesenteric arteries from stressed WKY rats, but not control WKY rats. Endothelium-independent relaxation to nitroprusside was impaired in vessels from stressed WKY rats, but not stressed BHR. Finally, contraction to phenylephrine was impaired in vessels from stressed BHR, but not WKY rats. In conclusion, changes in vascular reactivity induced by air-jet stress appear to correlate with, and may contribute to, the differential hemodynamic adaptations to stress observed in WKY rats and BHR.
β-Receptors and stress protein 70 expression in hypoxic myocardium of rainbow trout and chinook salmon
Authors: Gamperl A. K. , Vijayan M. M. , Pereira C. , Farrell A. P.
Published: December 2017

We examined the in vivo effect of acute hypoxemia on myocardial cell-surface (sarcolemmal) β-adrenoreceptor density (Bmax) and binding affinity ( KD) and on stress protein 70 (sp70) expression by exposing rainbow trout ( Oncorhynchus mykiss; 2.1–2.7 kg) to hypoxic water (3 mg/l O2) at 15°C for 6 h. This degree of hypoxia was the minimum O2level that these trout could tolerate without losing equilibrium and struggling violently. Hypoxic exposure reduced arterial [Formula: see text]([Formula: see text]) from 98 to 26 mmHg and arterial oxygen content ([Formula: see text]) from 10.8 to 7.4 vol/100 vol, but did not elevate epinephrine and norepinephrine levels above 10 and 30 nM, respectively. Despite the substantial reduction in blood oxygen status, the Bmaxand KDof myocardial cell-surface β-adrenoreceptors were unaffected by 6 h of hypoxic exposure. In addition, acute hypoxemia did not increase myocardial sp70 expression. The failure of short-term hypoxia to decrease trout myocardial β-adrenoreceptor density clearly contrasts with the established hypoxia-mediated downregulation shown for mammals. To further investigate the influence of low[Formula: see text] on salmonid myocardial β-adrenoreceptors, binding studies were performed on the spongy (continuously exposed to deoxygenated venous blood) and compact (perfused by oxygenated blood supplied by the coronary artery) myocardia of chinook salmon. The spongy myocardium has adapted to its microenvironment of continuous low[Formula: see text] by having 14% more cell-surface β-adrenoreceptors compared with the compact myocardium. There was no tissue-specific difference in KDand no evidence of sexual dimorphism in Bmaxor KD. We conclude from our studies that the salmonid heart is well adapted for sustained performance under hypoxic conditions. We found that wild chinook salmon had 2.8× more cell-surface β-adrenoreceptors compared with hatchery-reared rainbow trout. This difference suggests a significant degree of plasticity exists for fish myocardial β-adrenoreceptors. The signals underlying such differences await further study, but are not likely to include moderate hypoxia and sexual dimorphism.