bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium homeostasis in transplanted rats with a spontaneously hypertensive rat kidney
Authors: Frey Bernd A. J. , Grisk Olaf , Bandelow Norman , Wussow Siegfried , Bie Peter , Rettig Rainer
Published: December 2017

Recipients of a kidney from spontaneously hypertensive rats (SHR) but not from normotensive Wistar-Kyoto rats (WKY) develop posttransplantation hypertension. To investigate whether renal sodium retention precedes the development of posttransplantation hypertension in recipients of an SHR kidney on a standard sodium diet (0.6% NaCl), we transplanted SHR and WKY kidneys to SHR × WKY F1 hybrids, measured daily sodium balances during the first 12 days after removal of both native kidneys, and recorded mean arterial pressure (MAP) after 8 wk. Recipients of an SHR kidney ( n = 12) retained more sodium than recipients of a WKY kidney ( n = 12) (7.3 ± 10 vs. 4.0 ± 0.7 mmol, P < 0.05). MAP was 144 ± 6 mmHg in recipients of an SHR kidney and 106 ± 5 mmHg in recipients of a WKY kidney ( P < 0.01). Modest sodium restriction (0.2% NaCl) in a further group of recipients of an SHR kidney ( n = 10) did not prevent posttransplantation hypertension (MAP, 142 ± 4 mmHg). Urinary endothelin and urodilatin excretion rates were similar in recipients of an SHR and a WKY kidney. Transient excess sodium retention after renal transplantation may contribute to posttransplantation hypertension in recipients of an SHR kidney.
Role of the renin-angiotensin system in drinking of seawater-adapted eelsAnguilla japonica: a reevaluation
Authors: Takei Yoshio , Tsuchida Takamasa
Published: December 2017

The role of ANG II, a potent dipsogenic hormone, in copious drinking of seawater eels was examined. SQ-14225 (SQ), an angiotensin-converting enzyme inhibitor, infused intra-arterially at 0.01–1 μg · kg−1· min−1, depressed drinking and arterial blood pressure in a dose-dependent manner. The inhibition was accompanied by a small decrease in plasma ANG II concentration, which became significant at 1 μg · kg−1· min−1. After the infusate was changed back to the vehicle, the depression of drinking and arterial pressure continued for >2 h, although plasma ANG II concentration rebounded above the level before SQ infusion. By contrast, infusion of anti-ANG II serum (0.01–1 μg · kg−1· min−1) did not suppress drinking and arterial pressure, although plasma ANG II concentration decreased to undetectable levels. Plasma atrial natriuretic peptide and plasma osmolality, which influence drinking rate in eels, did not change during SQ or antiserum infusions. These results suggest that the renin-angiotensin system plays only a minor role in the vigorous drinking observed in seawater eels. The results also suggest that the antidipsogenic and vasodepressor effects of SQ in seawater eels are not due solely to the inhibition of ANG II formation in plasma.
Rapid induction of sodium appetite modifies taste-evoked activity in the rat nucleus of the solitary tract
Authors: McCaughey Stuart A. , Scott Thomas R.
Published: December 2017

Sodium-deprived rats develop a salt appetite and show changes in gustatory responses to NaCl in the periphery and brain stem; salt-sensitive neurons respond less to hypertonic NaCl than do corresponding cells in replete controls. By administering DOCA and renin, we generated a need-free sodium appetite quickly enough to permit us to monitor the activity of individual neurons in the nucleus of the solitary tract before and after its creation, permitting a more powerful within-subjects design. Subjects received DOCA pretreatment followed by an intracerebroventricular infusion of renin. In animals that were tested behaviorally, this resulted in elevated intake of 0.5 M NaCl. In neural recordings, renin caused decreased responding to hypertonic NaCl across all neurons and in the salt-sensitive neurons that were most responsive to NaCl before infusion. Most sugar-sensitive cells, in contrast, gave increased phasic responses to NaCl. These results confirm that sodium appetite is accompanied by decreased responding to NaCl in salt-sensitive neurons, complemented by increased activity in sugar-sensitive cells, even when created rapidly and independently of need.
Adaptation of the 24-h growth hormone profile to a state of sleep debt
Authors: Spiegel K. , Leproult R. , Colecchia E. F. , L'Hermite-Balériaux M. , Nie Z. , Copinschi G. , Van Cauter E.
Published: December 2017

In normal men, the majority of GH secretion occurs in a single large postsleep onset pulse that is suppressed during total sleep deprivation. We examined the impact of semichronic partial sleep loss, a highly prevalent condition, on the 24-h growth hormone profile. Eleven young men were studied after six nights of restricted bedtimes (0100–0500) and after 7 nights of extended bedtimes (2100–0900). Slow-wave sleep (SWS) was estimated as the duration of stages III and IV. Slow-wave activity (SWA) was calculated as electroencephalogram power density in the 0.5- to 3-Hz frequency range. During the state of sleep debt, the GH secretory pattern was biphasic, with both a presleep onset “circadian” pulse and a postsleep onset pulse. Postsleep onset GH secretion was negatively related to presleep onset secretion and tended to be positively correlated with the amount of concomitant SWA. When sleep was restricted, both SWS and SWA were increased during early sleep. Unexpectedly, the increase in SWA affected the second, rather than the first, SWA cycle, suggesting that presleep onset GH secretion may have limited SWA in the first cycle, possibly via an inhibition of central GH-releasing hormone activity. Thus neither the GH profile nor the distribution of SWA conformed with predictions from acute sleep deprivation studies, indicating that adaptation mechanisms are operative during chronic partial sleep loss.
Muscle oxygen kinetics at onset of intense dynamic exercise in humans
Authors: Bangsbo J. , Krustrup P. , González-Alonso J. , Boushel R. , Saltin B.
Published: December 2017

The present study examined the onset and the rate of rise of muscle oxidation during intense exercise in humans and whether oxygen availability limits muscle oxygen uptake in the initial phase of intense exercise. Six subjects performed 3 min of intense one-legged knee-extensor exercise [65.3 ± 3.7 (means ± SE) W]. The femoral arteriovenous blood mean transit time (MTT) and time from femoral artery to muscle microcirculation was determined to allow for an examination of the oxygen uptake at capillary level. MTT was 15.3 ± 1.8 s immediately before exercise, 10.4 ± 0.7 s after 6 s of exercise, and 4.7 ± 0.5 s at the end of exercise. Arterial venous O2difference (a-vdiffO2) of 18 ± 5 ml/l before the exercise was unchanged after 2 s, but it increased ( P < 0.05) after 6 s of exercise to 43 ± 10 ml/l and reached 146 ± 4 ml/l at the end of exercise. Thigh oxygen uptake increased ( P < 0.05) from 32 ± 8 to 102 ± 28 ml/min after 6 s of exercise and to 789 ± 88 ml/min at the end of exercise. The time to reach half-peak a-vdiffO2and thigh oxygen uptake was 13 ± 2 and 25 ± 3 s, respectively. The difference between thigh oxygen delivery (blood flow × arterial oxygen content) and thigh oxygen uptake increased ( P < 0.05) after 6 s and returned to preexercise level after 14 s. The present data suggest that, at the onset of exercise, oxygen uptake of the exercising muscles increases after a delay of only a few seconds, and oxygen extraction peaks after ∼50 s of exercise. The limited oxygen utilization in the initial phase of intense exercise is not caused by insufficient oxygen availability.
Excitation-induced Ca2+influx in rat soleus and EDL muscle: mechanisms and effects on cellular integrity
Authors: Gissel Hanne , Clausen Torben
Published: December 2017

In rat skeletal muscle, electrical stimulation increases Ca2+influx leading to progressive accumulation of calcium. Excitation-induced Ca2+influx in extensor digitorum longus (EDL; fast-twitch fibers) and soleus muscle (slow-twitch fibers) is compared. In EDL and soleus, stimulation at 40 Hz increased45Ca uptake 34- and 21-fold and22Na uptake 17- and 7-fold, respectively. These differences may be related to the measured 70% higher concentration of Na+channels in EDL. Repeated stimulation at 40 Hz elicited a delayed release of lactic acid dehydrogenase (LDH) from EDL (11-fold increase) and soleus (5-fold increase). Continuous stimulation at 1 Hz increased LDH release only from EDL (18-fold). This was associated with increased Ca2+content and was augmented at high extracellular Ca2+concentration ([Ca2+]o) and suppressed at low [Ca2+]o. The data support the hypothesis that excitation-induced Ca2+influx is mediated in part by Na+channels and that the ensuing increase in intracellular Ca2+induces cellular damage. This is most pronounced in EDL, which may account for the repeated observation that prolonged exercise leads to preferential damage to fast-twitch fibers.
Membrane mechanisms for electrogenic Na+-independentl-alanine transport in the lizard duodenal mucosa
Authors: Díaz Mario , Medina Virtudes , Gómez Tomás , Lorenzo Antonio
Published: December 2017

The active Na+-independent transport ofl-alanine across the duodenal mucosa of the lizard Gallotia galloti was studied in Ussing-type chambers using a computer-controlled voltage clamp. Addition of l-alanine to the Na+-free bathing solutions resulted in a significantl-alanine absorption ( Jnet) that was paralleled by an increase in transepithelial short-circuit current ( Isc) and potential difference (PD) without apparent changes in the tissue conductance. The concentration dependence of Jnet, PD, and Iscdisplayed Michaelis-Menten kinetics.l-alanine-induced electrical changes were completely inhibited by external alkaline pH or by the H+-ionophore carbonyl cyanide m-chlorophenyl-hydrazone in the bathing solution. The alanine-induced electrogenicity was dependent on the presence of extracellular K+and could be blocked by serosal Ba2+or mucosal orthovanadate. These results suggest the existence of an H+-coupledl-alanine cotransport at the apical membrane of enterocytes. The favorable H+driving force is likely to be maintained by an apical vanadate-sensitive H+-K+-ATPase, allowing the extrusion of H+in an exchange with K+. Potassium exit through a basolateral barium-sensitive conductance provides the key step for the electrogenicity of l-alanine absorption.
Racial differences in lipid metabolism in women with abdominal obesity
Authors: Racette Susan B. , Horowitz Jeffrey F. , Mittendorfer Bettina , Klein Samuel
Published: December 2017

We evaluated palmitate rate of appearance (Ra) in plasma during basal conditions and during a four-stage epinephrine infusion plus pancreatic hormonal clamp in nine white and nine black women with abdominal obesity, who were matched on fat-free mass, total and percent body fat, and waist-to-hip circumference ratio. On the basis of single-slice magnetic resonance imaging analysis, black women had the same amount of subcutaneous abdominal fat but less intra-abdominal fat than white women (68 ± 9 vs. 170 ± 14 cm2, P < 0.05). Basal palmitate Rawas lower in black than in white women (1.95 ± 0.26 vs. 2.88 ± 0.23 μmol · kg fat-free mass−1· min−1, P < 0.005), even though plasma insulin and catecholamine concentrations were the same in both groups. Palmitate Raacross a physiological range of plasma epinephrine concentrations remained lower in black women, because the increase in palmitate Raduring epinephrine infusion was the same in both groups. We conclude that basal and epinephrine-stimulated palmitate Rais lower in black than in white women with abdominal obesity. The differences in basal palmitate kinetics are not caused by alterations in plasma insulin or catecholamine concentrations or lipolytic sensitivity to epinephrine. The lower rate of whole body fatty acid flux and smaller intra-abdominal fat mass may have clinical benefits because of the relationship between excessive fatty acid availability and metabolic diseases.
Intense exercise causes decrease in expression of both endothelial NO synthase and tissue NOx level in hearts
Authors: Iemitsu Motoyuki , Miyauchi Takashi , Maeda Seiji , Yuki Koichi , Kobayashi Tsutomu , Kumagai Yoshito , Shimojo Nobuhiro , Yamaguchi Iwao , Matsuda Mitsuo
Published: December 2017

Cardiac myocytes produce nitric oxide (NO). We studied the effects of intense exercise on the expression of NO synthase (NOS) and the tissue level of nitrite (NO2−)/nitrate (NO3−) (i.e., NOx), which are stable end products of NO in the heart. Rats ran on a treadmill for 45 min. Immediately after this exercise, the heart was quickly removed. Control rats remained at rest during the same 45-min period. The mRNA level of endothelial NOS (eNOS) in the heart was markedly lower in the exercised rats than in the control rats. Western blot analysis confirmed downregulation of eNOS protein in the heart after exercise. Tissue NOx level in the heart was significantly lower in the exercised rats than in the control rats. The present study revealed for the first time that production of NO in the heart is decreased by intense exercise. Because NO attenuates positive inotropic and chronotropic responses to β1-adrenergic stimulation in the heart, the decrease in cardiac production of NO by intense exercise may contribute to the acceleration of increase in myocardial contractility and heart rate during intense exercise.
Vagal CCK and 5-HT3receptors are unlikely to mediate LPS or IL-1β-induced fever
Authors: Martin S. M. , Wilson B. C. , Chen X. , Takahashi Y. , Poulin P. , Pittman Q. J.
Published: December 2017

Previous studies suggested that peripheral immune mediators may involve intermediates acting on the vagus nerve, such as CCK or serotonin (5-HT). We have therefore investigated a possible role for vagal CCK-A and 5-HT3receptors in the febrile response after intraperitoneal human recombinant interleukin-1β (IL-1β) or lipopolysaccharide (LPS). Unanesthetized, adult male rats instrumented with abdominal thermistors were given intraperitoneal CCK-8 sulfate (100 or 150 μg/kg) or 2-methyl-5-hydroxytryptamine maleate (4 mg/kg). In other experiments, rats were treated with either antagonists to the 5-HT3 receptor (ondansetron HCl; 100 μg/kg) or the CCK-A receptor (L-364,718, 100 or 200 μg/kg) in combination with LPS or IL-1β. CCK administration caused a short-lived hypothermia, but interference with the action of endogenous CCK at CCK-A receptors was without effect on IL-1β- or LPS-induced fever. Neither activation of 5-HT3 receptors nor blockade of 5-HT3 receptors affected body temperature or LPS fever. Taken together, our data support the idea that vagal afferents responsive to pyrogenic cytokines may be different from those responsive to CCK or 5-HT.
Leukocyte-endothelial cell interactions in diabetic retina after transient retinal ischemia
Authors: Tsujikawa Akitaka , Kiryu Junichi , Nonaka Atsushi , Yamashiro Kenji , Nishiwaki Hirokazu , Honda Yoshihito , Ogura Yuichiro
Published: December 2017

Diabetes is associated with increased neural damage after transient cerebral ischemia. Recently, leukocytes, which are thought to play a central role in ischemia-reperfusion injury, have been suggested to be involved in exacerbated damage after transient ischemia in diabetic animals. The present study was designed to clarify whether the anticipated worse outcome after transient cerebral ischemia in diabetic animals was due to augmented leukocyte-mediated neural injury. Using rats with streptozotocin-induced diabetes of 4-wk duration, we investigated leukocyte-endothelial cell interactions during reperfusion after a transient 60-min period of retinal ischemia. Unexpectedly, postischemic diabetic retina showed no active leukocyte-endothelial cell interactions during reperfusion. The maximal numbers of rolling and accumulating leukocytes in diabetic retina were reduced by 73.6 and 41.2%, respectively, compared with those in nondiabetic rats. In addition, neither preischemic insulin treatment of diabetic rats nor preischemic glucose infusion of nondiabetic rats significantly influenced leukocyte-endothelial cell interactions during reperfusion. The present study demonstrated that high blood glucose concentration before induction of ischemia did not exacerbate leukocyte involvement in the postischemic retinal injury. Furthermore, diabetic retina showed suppressed leukocyte-endothelial cells interactions after transient ischemia, perhaps due to an adaptive mechanism that developed during the period of induced diabetes.
Differential effects of selective vagotomy and tropisetron in aminoprivic feeding
Authors: Dixon Kimberly D. , Williams Fred E. , Wiggins Raymond L. , Pavelka Jason , Lucente James , Bellinger Larry L. , Gietzen Dorothy W.
Published: December 2017

Both total subdiaphragmatic vagotomy (TVAGX) and serotonin3 receptor blockade with tropisetron or ondansetron attenuate amino acid-imbalanced diet (Imb) anorexia. Total vagotomy is less effective than tropisetron in reducing Imb-induced anorexia and also blunts the tropisetron effect. With the use of electrocautery at the subdiaphragmatic level of the vagus, we severed the ventral and dorsal trunks as well as the hepatic, ventral gastric, dorsal gastric, celiac, and accessory celiac branches separately or in combination to determine which vagal branches or associated structures may be involved in these responses. Rats were prefed a low-protein diet. On the first experimental day, tropisetron or saline was given intraperitoneally 1 h before presentation of Imb. Cuts including the ventral branch, i.e., TVAGX, ventral vagotomy (above the hepatic branch), and hepatic + gastric vagotomies (but not hepatic branch cuts alone) caused the highest ( P < 0.05) Imb intake on day 1 with or without tropisetron. The responses to tropisetron were not affected significantly. On days 2–8, groups having vagotomies that included the hepatic branch recovered faster than sham-treated animals. Because the hepatic and gastric branches together account for most of the vagal innervation to the proximal duodenum, this area may be important in the initial responses, whereas structures served by the hepatic branch alone apparently act in the later adaptation to Imb.
Hematological changes and athletic performance in horses in response to high altitude (3,800 m)
Authors: Wickler Steven J. , Anderson Timothy P.
Published: December 2017

This study had two goals: 1) measure hematologic changes with high-altitude acclimatization in horses; and 2) assess the effect of 9 days at high altitude on subsequent athletic performance at low altitude. Six horses performed standardized exercise tests on a dirt track (before and during time at altitude) and treadmill (pre- and postaltitude exposure). Resting and immediate postexercise blood samples were measured for blood volume, lactate, red cell number, packed cell volume, and 2,3-diphosphoglycerate (DPG) concentrations at 225 m, over a 9-day period at 3,800 m, and shortly after returning to 225 m. Acclimatization produced increases in total red cell volume (38.2 ± 2.4 to 48.1 ± 2.9 ml/kg, P = 0.004) and DPG/hemoglobin concentrations (19.4 ± 1.7 increased to 29.4 ± 0.4 μmol/g, P = 0.004). Two performance variables, heart rate recovery postexercise and lactate recovery, were faster after acclimatization.
Metabolic depression and enhanced O2affinity of mitochondria in hypoxic hypometabolism
Authors: St-Pierre Julie , Tattersall Glenn J. , Boutilier Robert G.
Published: December 2017

This study examined whether the steady-state hypometabolism seen in overwintering frogs ( Rana temporaria) is reflected at the mitochondrial level either by a reduction in their resting (state 4) and active (state 3) respiration rates and/or by increases in O2affinity. We isolated mitochondria from the skeletal muscle of cold-submerged frogs at different stages during their hibernation in normoxic and hypoxic water. A modest metabolic depression at the whole animal level (normoxic submergence) was not associated with a reduction in mitochondrial state 4 and state 3 respiration rates. However, mitochondria isolated from frogs that were submerged for 1 mo manifested an increase in their O2affinity compared with controls and with animals submerged for 4 mo. Hypometabolism was more pronounced at the whole animal level during hypoxic submergence and was accompanied by 1) a reduction in mitochondrial state 4 and state 3 rates and 2) an increase in the O2affinity of mitochondria. These findings demonstrate that metabolic depression can be reflected at all levels of biological organization in hypoxia-tolerant animals.
GABAergic contribution to rat bladder hyperactivity after middle cerebral artery occlusion
Authors: Kanie Sayoko , Yokoyama Osamu , Komatsu Kazuto , Kodama Koichi , Yotsuyanagi Satoshi , Niikura Susumu , Nagasaka Yasuhiro , Miyamoto Ken-Ichi , Namiki Mikio
Published: December 2017

To evaluate the influences of γ-aminobutyric acid (GABA) mechanisms on bladder hyperactivity after left middle cerebral artery occlusion, cystometric recordings were obtained from unanesthetized female rats. Intracerebroventricular administration of both muscimol (GABAA receptor agonist; 0.1–10 nmol) and baclofen (GABAB receptor agonist; 0.1–3 nmol) produced dose-dependent inhibitions of micturition with increases in bladder capacity (BC). The effects of high doses (1–10 nmol) were similar in sham-operated (SO) and cerebral-infarcted (CI) rats. However, lower doses of muscimol (0.1 or 0.3 nmol) and baclofen (0.1 nmol) reduced BC in CI rats. After bicuculline (GABAA receptor antagonist; 1 or 3 nmol) administration, BC in both SO and CI rats first decreased and subsequently increased. An increase in urethral pressure was observed after administration of bicuculline (3 nmol) but not with either muscimol or baclofen. Infarct volumes in muscimol-, bicuculline-, or baclofen-treated rats were not significantly different from those of vehicle-treated rats. These results suggest that GABAergic mechanisms inhibit the micturition reflex at the supraspinal level but that this can change as a result of CI.
Angiotensin II infusion to the midgestation ovine fetus: effects on the fetal kidney
Authors: Moritz Karen , Koukoulas Irene , Albiston Anthony , Wintour E. Marelyn
Published: December 2017

Renal and cardiovascular responses to an intravenous infusion of ANG II (1 μg/h) or saline for 3 days were examined in ovine fetuses at midgestation (75–85 days of gestation, term 150 days). ANG II caused an increase in fetal blood pressure (36 ± 2 to 44 ± 3 mmHg) and urine flow rate (8 ± 2 to a maximum of 18 ± 6 ml/h). Plasma renin concentrations decreased in ANG II-infused fetuses. Fetal fluids (amniotic and allantoic) did not differ in volume or composition between the groups when measured at postmortem. There was no difference in the expression levels of the mRNA for the angiotensin (AT1or AT2) receptors between the two groups when measured by an RNase protection assay. However, there was a significant decline in renin and AT1receptor gene expression when measured by a real-time polymerase chain reaction method. These results indicate that ANG II is diuretic and pressor when infused at midgestation. ANG II can feedback to decrease renin secretion by the fetal kidney, and this may occur by decreased renin gene expression.
Impact of gender and endothelin on renal vasodilation and hyperfiltration induced by relaxin in conscious rats
Authors: Danielson Lee A. , Kercher Laurie J. , Conrad Kirk P.
Published: December 2017

Chronic administration of the hormone relaxin elicits renal vasodilation that is dependent on nitric oxide (NO) in both conscious intact and ovariectomized female rats. Our first objective was to test whether the hormone, when administered to approximate serum concentrations found in midterm pregnant rats, induces renal vasodilation in males. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) increased significantly, on average, by 33 and 49% over baseline, respectively, after 5 days of recombinant human relaxin (rhRLX) administration to 12 conscious male rats by subcutaneous osmotic minipump. There were also significant decreases in hematocrit, plasma osmolality, and sodium concentration. Another objective was to determine whether endogenous endothelin (ET; via the endothelial ETB receptor) mediates the NO-dependent renal vasodilation produced by relaxin. rhRLX or vehicle was administered to conscious female rats ( n = 9 and 8 rats, respectively). On the fifth day, baseline GFR and ERPF were both increased, on average, by 20–30% in the rats administered rhRLX ( P < 0.05 vs. vehicle). Next, the specific ETB-receptor antagonist RES-701-1 was infused intravenously over 4 h in both groups of rats. In response to RES-701-1, there was a significant decline in both GFR and ERPF in the rats receiving rhRLX such that renal function converged in the two groups of animals. We conclude 1) relaxin induces marked changes in the renal circulation and in osmoregulation regardless of gender and 2) relaxin-induced renal vasodilation and hyperfiltration are mediated by endothelin through the endothelial ETB receptor subtype and NO.
Effect of neonatal hypoxia on the development of hepatic lipase in the rat
Authors: Lee Ping C. , Jelinek Beth , Struve Mark , Bruder Eric D. , Raff Hershel
Published: December 2017

Increases in plasma lipids occur during hypoxia in suckling but not in weaned rats and may result from altered hepatic enzyme activity. We exposed rats to 7 days of hypoxia from birth to 7 days of age (suckling) or from 28 to 35 days of age (weaned at day 21). Hypoxia led to an increase in hepatic lipid content in the suckling rat only. Hepatic lipase was decreased to ∼45% of control in 7-day-old rats exposed to hypoxia but not in hypoxic 35-day-old rats. Hypoxic suckling rats also had a 50% reduction in lactate dehydrogenase activity, whereas transaminase activity and CYP1A and CYP3A protein content were not different between hypoxic and normoxic groups. Additional rats were studied 7 and 14 days after recovery from hypoxic exposure from birth to 7 days of age; hepatic lipase activity had recovered to 85% by 7 days and to 100% by 14 days in the rats previously exposed to hypoxia. Administration of dexamethasone to neonatal rats to simulate the hyperglucocorticoid state found in hypoxic 7-day-old rats led to a moderate decrease (∼75% of control) in hepatic lipases. Developmentally, in the normoxic state, hepatic lipases increased rapidly after birth and reached levels more than twofold that of the newborn by 7 days of age. Hypoxia delays the maturation of hepatic lipases. We suggest that the decrease in hepatic lipase activity contributes to hyperlipemia in the hypoxic newborn rats.
Dual role of PKC in modulating pharmacomechanical coupling in fetal and adult cerebral arteries
Authors: Longo Lawrence D. , Zhao Yu , Long Wen , Miguel Carolyn , Windemuth Ryan S. , Cantwell Anne-Maree , Nanyonga Alice T. , Saito Tsuyoshi , Zhang Lubo
Published: December 2017

This study tested the hypothesis that protein kinase C (PKC) has dual regulation on norepinephrine (NE)-mediated inositol 1,4,5-trisphosphate [Ins (1,4,5)P3] pathway and vasoconstriction in cerebral arteries from near-term fetal (∼140 gestational days) and adult sheep. Basal PKC activity values (%membrane bound) in fetal and adult cerebral arteries were 38 ± 4% and 32 ± 4%, respectively. In vessels of both age groups, the PKC isoforms α, βI, βII, and δ were relatively abundant. In contrast, compared with the adult, cerebral arteries of the fetus had low levels of PKC-ε. In response to 10−4M phorbol 12,13-dibutyrate (PDBu; PKC agonist), PKC activity in both fetal and adult cerebral arteries increased 40–50%. After NE stimulation, PKC activation with PDBu exerted negative feedback on Ins(1,4,5)P3and intracellular Ca2+concentration ([Ca2+]i) in arteries of both age groups. In turn, PKC inhibition with staurosporine resulted in augmented NE-induced Ins(1,4,5)P3and [Ca2+]iresponses in adult, but not fetal, cerebral arteries. In adult tissues, PKC stimulation by PDBu increased vascular tone, but not [Ca2+]i. In contrast, in the fetal artery, PKC stimulation was associated with an increase in both tone and [Ca2+]i. In the presence of zero extracellular [Ca2+], these PDBu-induced responses were absent in the fetal vessel, whereas they remained unchanged in the adult. We conclude that, although basal PKC activity was similar in fetal and adult cerebral arteries, PKC's role in NE-mediated pharmacomechanical coupling differed significantly in the two age groups. In both fetal and adult cerebral arteries, PKC modulation of NE-induced signal transduction responses would appear to play a significant role in the regulation of vascular tone. The mechanisms differ in the two age groups, however, and this probably relates, in part, to the relative lack of PKC-ε in fetal vessels.
Synergy ofl-arginine and growth hormone (GH)-releasing peptide-2 on GH release: influence of gender
Authors: Wideman Laurie , Weltman Judy Y. , Patrie James T. , Bowers C. Y. , Shah Niki , Story Shannon , Weltman Arthur , Veldhuis Johannes D.
Published: December 2017

We test the hypotheses that 1) growth hormone (GH)-releasing peptide-2 (G) synergizes with l-arginine (A), a compound putatively achieving selective somatostatin withdrawal and 2) gender modulates this synergy on GH secretion. To these ends, 18 young healthy volunteers (9 men and 9 early follicular phase women) each received separate morning intravenous infusions of saline (S) or A (30 g over 30 min) or G (1 μg/kg) or both, in randomly assigned order. Blood was sampled at 10-min intervals for later chemiluminescence assay of serum GH concentrations. Analysis of covariance revealed that the preinjection (basal) serum GH concentrations significantly determined secretagogue responsiveness and that sex ( P = 0.02) and stimulus type ( P < 0.001) determined the slope of this relationship. Nested ANOVA applied to log-transformed measures of GH release showed that gender determines 1) basal rates of GH secretion, 2) the magnitude of the GH secretory response to A, 3) the rapidity of attaining the GH maximum, and 4) the magnitude or fold (but not absolute) elevation in GH secretion above preinjection basal, as driven by the combination of A and G. In contrast, the emergence of the G and A synergy is sex independent. We conclude that gender modulates key facets of basal and A/G-stimulated GH secretion in young adults.
Gastrointestinal motility during pregnancy: role of nitrergic component of NANC nerves
Authors: Shah Sangita , Hobbs Adrian , Singh Rajan , Cuevas Janis , Ignarro Louis J. , Chaudhuri Gautam
Published: December 2017

This study evaluated whether increased release of nitric oxide (NO) from the nitrergic component of the nonadrenergic, noncholinergic (NANC) nerves may be partly responsible for the decrease in gastrointestinal motility observed during pregnancy. Segments of fundal strip, ileum, and colon were obtained from nonpregnant rats, rats in midpregnancy ( days 9–11), and rats in late pregnancy ( days 18–20). NANC activity was studied by assessing changes in tone after application of electric field stimulation (EFS). The role of NO was determined by observing the effects of EFS in the presence and absence of the NO synthase (NOS) inhibitor N G-nitro-l-arginine methyl ester (l-NAME) and the reversibility of the effects ofl-NAME by l-arginine. The magnitude of change in cGMP levels in the tissues after application of EFS was also assessed. Our studies indicate that there was increased magnitude of relaxation of isolated strips of rat gastric fundus and rat colon, after application of EFS to tissues obtained only from animals in late pregnancy. These results paralleled the changes in cGMP levels in tissues. NOS activity in the gastric fundus was significantly increased in animals in late pregnancy compared with nonpregnant controls. Our studies suggest that the delay in gastric emptying and increase in colonic transit time observed in rats during pregnancy may be caused in part by increased activity of the nitrergic component of the NANC nerves innervating these organs.
Opioids affect acquisition of LiCl-induced conditioned taste aversion: involvement of OT and VP systems
Authors: Olszewski Pawel K. , Shi Qiuying , Billington Charles J. , Levine Allen S.
Published: December 2017

Aversive properties of lithium chloride (LiCl) are mediated via pathways comprising neurons of the nucleus of the solitary tract (NTS) and oxytocin (OT) and vasopressin (VP) cells in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Because opioids act on brain regions that mediate effects of LiCl, we evaluated whether administration of opioids shortly before LiCl in rats influences 1) development of conditioned taste aversion (CTA) and 2) activation of NTS neurons and OT/VP cells. Neuronal activation was assessed by applying c-Fos immunohistochemical staining. Three opioids were used: morphine (MOR), a μ-agonist, butorphanol tartrate (BT), a mixed μ/κ-agonist, and nociceptin/orphanin FQ (N/OFQ), which binds to an ORL1 receptor. BT and N/OFQ completely blocked acquisition of CTA. MOR alleviated but did not eliminate the aversive effects. Each of the opioids decreased LiCl-induced activation of NTS neurons as well as OT and VP cells in the PVN and SON. We conclude that opioids antagonize aversive properties of LiCl, presumably by suppressing activation of pathways that encompass OT and VP cells and NTS neurons.
Induction of BGT-1 and amino acid System A transport activities in endothelial cells exposed to hyperosmolarity
Authors: Petronini Pier-Giorgio , Alfieri Roberta R. , Losio M. Nadia , Caccamo Alessandro E. , Cavazzoni Andrea , Bonelli Mara A. , Borghetti Angelo F. , Wheeler Kenneth P.
Published: December 2017

We studied the responses to hypertonicity of cultured endothelial cells from swine pulmonary arteries. In 0.5 osmol/kgH2O medium, initial cell shrinkage was followed by a regulatory volume increase (RVI), complete after 1 h, concomitant with an increase in cellular K+content. Then the activity of amino acid transport System A increased, accompanied by an accumulation of ninhydrin-positive solutes (NPS), reaching a peak at ∼6 h. The subsequent decline in System A activity was paralleled by an induction of the betaine-GABA transporter (BGT-1), detected as increases of BGT-1 mRNA and of transport activity, which peaked at ∼24 h. Inhibitors of transcription or translation prevented induction of both transport activities. The increased expression of BGT-1, which involved activation of “tonicity-responsive enhancer,” was inhibited by 5 mM extracellular betaine. Cellular K+concentration gradually declined after the accumulation of NPS and during the induction of BGT-1. This very effective adaptation to hypertonicity suggests it has a physiological role.
17β-Estradiol prevents oxidative stress and decreases blood pressure in ovariectomized rats
Authors: Hernández Isabel , Delgado Juan L. , Díaz Julian , Quesada Tomas , Teruel M. José G. , Llanos M. Carmen , Carbonell Luis F.
Published: December 2017

In this study, we tested whether estrogen deficiency is associated with oxidative stress and decreased nitric oxide (NO) production, which could be responsible for an increased blood pressure in ovariectomized rats. Hemodynamic studies were performed on conscious, chronically instrumented rats. Chronic estrogen replacement on ovariectomized rats lowered blood pressure ∼13 mmHg, from 119 ± 3 mmHg in ovariectomized rats to 106 ± 3 mmHg in ovariectomized-treated rats; it was also accompanied by an increase in cardiac index and vascular conductance, achieving hemodynamic values similar to those shown by sham-operated rats. N G-nitro-l-arginine methyl ester administration lowered significantly less the vascular conductance (0.14 ± 0.01 vs. 0.22 ± 0.03 and 0.26 ± 0.01 ml · min−1 · mmHg−1/100 g; P < 0.05) in ovariectomized rats than in the sham-operated and estrogen-treated ovariectomized rats, respectively. Estrogen replacement prevented the lower plasma levels of nitrites/nitrates observed in ovariectomized rats. The lower plasma total antioxidant status and reduced thiol groups and the increase in plasma lipoperoxides presented in ovariectomized animals were reestablished with the estrogen treatment. These results show that estrogen administration decreases blood pressure and increases vascular conductance in ovariectomized rats. This effect may be related to an increase in NO synthesis and/or preventing oxidative stress, then improving endothelial function.
An l-proline-dependent proton flux is located at the apical membrane level of the eel enterocytes
Authors: Ingrosso L. , Marsigliante S. , Zonno V. , Storelli C. , Vilella S.
Published: December 2017

This study has demonstrated the existence of an l-proline-dependent (Na independent) proton flux at the apical membrane level of the eel intestinal absorbing cells. Using isolated eel enterocytes and the pH-sensitive fluorescent dye 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF), it was shown that a 20 mM concentration of the imino acid l-proline in the extracellular medium determined an intracellular acidification of ∼0.28 pH units. However, neither sucrose nor other amino acids were able to significantly acidify the resting intracellular pH. A hyperbolic relationship between extracellular proline concentration and intracellular proton accumulation was observed. Using both isolated brush-border and basolateral membrane vesicles, it was demonstrated that this proline-proton cotransport mechanism was located at the apical membrane level only. In addition, the existence of a coupling mechanism between proline and proton fluxes was demonstrated by the observation that, in brush-border membrane vesicles, the presence of a pH gradient (pHin > pHout) stimulated the uptake ofl-proline.
Potassium channels in primary cultures of seawater fish gill cells. II. Channel activation by hypotonic shock
Authors: Duranton C. , Mikulovic E. , Tauc M. , Avella M. , Poujeol P.
Published: December 2017

Previous studies performed on apical membranes of seawater fish gills in primary culture have demonstrated the existence of stretch-activated K+channels with a conductance of 122 pS. The present report examines the involvement of K+channels in ion transport mechanisms and cell swelling. In the whole cell patch-clamp configuration, K+currents were produced by exposing cells to a hypotonic solution or to 1 μM ionomycin. These K+currents were inhibited by the addition of quinidine and charybdotoxin to the bath solution. Isotopic efflux measurements were performed on cells grown on permeable supports using86Rb+as a tracer to indicate potassium movements. Apical and basolateral membrane86Rb effluxes were stimulated by the exposure of cells to a hypotonic medium. During the hypotonic shock, the stimulation of86Rb efflux on the apical side of the monolayer was inhibited by 500 μM quinidine or 100 μM gadolinium but was insensitive to scorpion venom [ Leirus quinquestriatus hebraeus (LQH)]. An increased86Rb efflux across the basolateral membrane was also reduced by the addition of quinidine and LQH venom but was not modified by gadolinium. Moreover, basolateral and apical membrane86Rb effluxes were not modified by bumetanide or thapsigargin. There is convincing evidence for two different populations of K+channels activated by hypotonic shock. These populations can be separated according to their cellular localization (apical or basolateral membrane) and as a function of their kinetic behavior and pharmacology.
Ca2+binding to cardiac troponin C: effects of temperature and pH on mammalian and salmonid isoforms
Authors: Gillis Todd E. , Marshall Christian R. , Xue Xiao-Hua , Borgford Thor J. , Tibbits Glen F.
Published: December 2017

A reduction in temperature lowers the Ca2+sensitivity of skinned cardiac myofilaments but this effect is attenuated when native cardiac troponin C (cTnC) is replaced with skeletal TnC. This suggests that conformational differences between the two isoforms mediate the influence of temperature on contractility. To investigate this phenomenon, the functional characteristics of bovine cTnC (BcTnC) and that from rainbow trout, Oncorhynchus mykiss, a cold water salmonid (ScTnC), have been compared. Rainbow trout maintain cardiac function at temperatures cardioplegic to mammals. To determine whether ScTnC is more sensitive to Ca2+than BcTnC, F27W mutants were used to measure changes in fluorescence with in vitro Ca2+titrations of site II, the activation site. When measured under identical conditions, ScTnC was more sensitive to Ca2+than BcTnC. At 21°C, pH 7.0, as indicated by K1/2(−log[Ca] at half-maximal fluorescence, where [Ca] is calcium concentration), ScTnC was 2.29-fold more sensitive to Ca2+than BcTnC. When pH was kept constant (7.0) and temperature was lowered from 37.0 to 21.0°C and then to 7.0°C, the K1/2of BcTnC decreased by 0.13 and 0.32, respectively, whereas the K1/2of ScTnC decreased by 0.76 and 0.42, respectively. Increasing pH from 7.0 to 7.3 at 21.0°C increased the K1/2of both BcTnC and ScTnC by 0.14, whereas the K1/2of both isoforms was increased by 1.35 when pH was raised from 7.0 to 7.6 at 7.0°C.
Interaction of SKCachannels and L-type Ca2+channels in catecholamine secretion in the rat adrenal gland
Authors: Nagayama Takahiro , Fukushima Yasuo , Hikichi Hirohiko , Yoshida Makoto , Suzuki-Kusaba Mizue , Hisa Hiroaki , Kimura Tomohiko , Satoh Susumu
Published: December 2017

We elucidated the interaction of small-conductance Ca2+-activated K+(SKCa) channels and L-type Ca2+channels in muscarinic receptor-mediated control of catecholamine secretion in the isolated perfused rat adrenal gland. The muscarinic agonist methacholine (10–300 μM) produced concentration-dependent increases in adrenal output of epinephrine and norepinephrine. The SKCachannel blocker apamin (1 μM) enhanced the methacholine-induced catecholamine responses. The facilitatory effect of apamin on the methacholine-induced catecholamine responses was not observed during treatment with the L-type Ca2+channel blocker nifedipine (3 μM) or Ca2+-free solution. Nifedipine did not affect the methacholine-induced catecholamine responses, but it inhibited the responses during treatment with apamin. The L-type Ca2+channel activator Bay k 8644 (1 μM) enhanced the methacholine-induced catecholamine responses, whereas the enhancement of the methacholine-induced epinephrine and norepinephrine responses were prevented and attenuated by apamin, respectively. These results suggest that SKCachannels are activated by muscarinic receptor stimulation, which inhibits the opening of L-type Ca2+channels and thereby attenuates adrenal catecholamine secretion.
Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats
Authors: Schreihofer Ann M. , Guyenet Patrice G.
Published: December 2017

The rostral ventrolateral medulla (RVLM) may play an important role in the sympatholytic and hypotensive effects of clonidine. The present study examined which type of presympathetic RVLM neuron is inhibited by clonidine, and whether the adrenergic presympathetic RVLM neurons are essential for clonidine-induced sympathoinhibition. In chloralose-anesthetized and ventilated rats, clonidine (10 μg/kg iv) decreased arterial pressure (116 ± 6 to 84 ± 2 mmHg) and splanchnic nerve activity (93 ± 3% from baseline). Extracellular recording and juxtacellular labeling of barosensitive bulbospinal RVLM neurons revealed that most cells were inhibited by clonidine (26/28) regardless of phenotype [tyrosine hydroxylase (TH)-immunoreactive cells: 48 ± 7%; non-TH-immunoreactive cells: 42 ± 5%], although the inhibition of most neurons was modest compared with the observed sympathoinhibition. Depletion of most bulbospinal catecholaminergic neurons, including 76 ± 5% of the rostral C1 cells, by microinjection of saporin anti-dopamine β-hydroxylase into the thoracic spinal cord (levels T2 and T4, 42 ng · 200 nl−1 · side−1) did not alter the sympatholytic or hypotensive effects of clonidine. These data show that although clonidine inhibits presympathetic C1 neurons, bulbospinal catecholaminergic neurons do not appear to be essential for the sympatholytic and hypotensive effects of systemically administered clonidine. Instead, the sympatholytic effect of clonidine is likely the result of a combination of effects on multiple cell types both within and outside the RVLM.
Activity and responsiveness of the renin-angiotensin system in the aging rat
Authors: Thompson Michele M. , Oyama Terry T. , Kelly Francis J. , Kennefick Thomas M. , Anderson Sharon
Published: December 2017

The systemic renin-angiotensin system (RAS) is suppressed in normal aging, but the activity of the tissue RAS is not well defined. We examined the systemic and intrarenal RAS status of aging normal rats and responses to suppression and stimulation of the production of endogenous ANG II. Studies were performed in young (3 mo) and early aging (15 mo) male Sprague-Dawley rats. Angiotensin-converting enzyme inhibitors modestly decreased mean arterial pressure (MAP) in young (3 mo) and early aging (15 mo) rats and limited proteinuria in the older rats. There were no significant age-related effects on renal function or on endogenous RAS activity. Intravenous infusion of the precursor ANG I led to comparable increases in MAP in younger and older rats. In contrast, the renal effects (reduction in glomerular filtration and plasma flow rates) were exaggerated in the older animals. Intrarenal arterial ANG I did not affect MAP in any group. In young rats, there were no significant hemodynamic effects in either the ipsilateral (infused) or the contralateral (noninfused) kidney. In the older rats, both kidneys had a significant fall in renal renal plasma flow rate (RPF) with left renal arterial infusion of ANG I. Accordingly, these studies early in the course of aging found only subtle changes in the activity, responsiveness, and metabolism of the RAS. Thus early aging is associated with a modest but important increase in sensitivity to RAS stimulation.
Ingested water equilibrates isotopically with the body water pool of a shorebird with unrivaled water fluxes
Authors: Visser G. Henk , Dekinga Anne , Achterkamp Bart , Piersma Theunis
Published: December 2017

We investigated the applicability of 2H to measure the amount of body water (TBW) and water fluxes in relation to diet type and level of food intake in a mollusk-eating shorebird, the Red Knot ( Calidris canutus). Six birds were exposed to eight experimental indoor conditions. Average fractional 2H turnover rates ranged between 0.182 day−1 (SD = 0.0219) for fasting birds and 7.759 day−1 (SD = 0.4535) for birds feeding on cockles ( Cerastoderma edule). Average TBW estimates obtained with the plateau method were within the narrow range of 75.9–85.4 g (or between 64.6 and 70.1% of the body mass). Those obtained with the extrapolation method showed strong day-to-day variations (range 55.7–83.7 g, or between 49.7 and 65.5%). Average difference between the two calculation methods ranged between 0.6% and 36.3%, and this difference was strongly negatively correlated with water flux rate. Average water influx rates ranged between 15.5 g/day (fasting) and 624.5 g/day (feeding on cockles). The latter value is at 26.6 times the allometrically predicted value and is the highest reported to date. Differences in 2H concentrations between the blood and feces (i.e., biological fractionation) were small but significant (−3.4% when fed a pellet diet, and −1.1% for all the other diets), and did not relate to the rate of water flux (χ2 1 = 0.058, P < 0.81). We conclude that the ingested water equilibrated rapidly with the body water pool even in an avian species that shows record water flux rates when living on ingested marine bivalves.