bluuebunny/crossref_metadata_2025 huggingface dataset:
Episodic hypoxia enhances late hypoxic ventilation in developing rat: putative role of neuronal NO synthase
Authors: Gozal David , Gozal Evelyne
Published: December 2017

Nitric oxide (NO) is an excitatory neurotransmitter in the hypoxic ventilatory response (HVR). Furthermore, neuronal NO synthase (nNOS) activity in the developing rat correlates with the magnitude of late hypoxic ventilatory depression. To test the hypothesis that repeated short exposures to hypoxia may modify late HVR characteristics in young rats, we conducted 30-min hypoxic challenges in 2- to 3-day-old rat pups, before (Pre) and 6 h after (Post) they completed a series of eight cycles consisting of 5 min of hypoxia and 10 min of normoxia (Hyp-Norm) or normoxia throughout (Norm-Norm). In an additional group, similar challenges were performed after administration of either intraperitoneal vehicle or 25 mg/kg 7-nitroindazole (7-NI). Ventilation (V˙e) was measured using whole body plethysmography. Although no changes in peakV˙e responses occurred with episodic hypoxia (Pre vs. Post, P = not significant), lateV˙e reductions were markedly attenuated in Post (ΔV˙e from early to late: 7.2 ± 1.5 ml/min in Pre vs. 4.5 ± 1.1 ml/min in Post; P < 0.002). Furthermore, 7-NI treatment of Post animals was associated with lateV˙e reductions to Pre levels in Hyp-Norm-exposed animals. Western blots of protein equivalents from the caudal brain stem revealed increased nNOS expression in Hyp-Norm compared with Norm-Norm ( P < 0.01). Current findings suggest that repeated short hypoxic exposures improve the ability to sustain V˙e, which appears to be mediated by increased nNOS expression and activity in brain stem respiratory regions. We postulate that changes in nNOS may play a role in respiratory control plasticity.
Hyperinsulinemia produces cardiac vagal withdrawal and nonuniform sympathetic activation in normal subjects
Authors: Van De Borne Philippe , Hausberg Martin , Hoffman Robert P. , Mark Allyn L. , Anderson Erling A.
Published: December 2017

The exact mechanisms for the decrease in R-R interval (RRI) during acute physiological hyperinsulinemia with euglycemia are unknown. Power spectral analysis of RRI and microneurographic recordings of muscle sympathetic nerve activity (MSNA) in 16 normal subjects provided markers of autonomic control during 90-min hyperinsulinemic/euglycemic clamps. By infusing propranolol and insulin ( n = 6 subjects), we also explored the contribution of heightened cardiac sympathetic activity to the insulin-induced decrease in RRI. Slight decreases in RRI ( P < 0.001) induced by sevenfold increases in plasma insulin could not be suppressed by propranolol. Insulin increased MSNA by more than twofold ( P < 0.001), decreased the high-frequency variability of RRI ( P< 0.01), but did not affect the absolute low-frequency variability of RRI. These results suggest that reductions in cardiac vagal tone and modulation contribute at least in part to the reduction in RRI during hyperinsulinemia. Moreover, more than twofold increases in MSNA occurring concurrently with a slight and not purely sympathetically mediated tachycardia suggest regionally nonuniform increases in sympathetic activity during hyperinsulinemia in humans.
Age, splanchnic vasoconstriction, and heat stress during tilting
Authors: Minson Christopher T. , Wladkowski Stacey L. , Pawelczyk James A. , Kenney W. Larry
Published: December 2017

During upright tilting, blood is translocated to the dependent veins of the legs and compensatory circulatory adjustments are necessary to maintain arterial pressure. For examination of the effect of age on these responses, seven young (23 ± 1 yr) and seven older (70 ± 3 yr) men were head-up tilted to 60° in a thermoneutral condition and during passive heating with water-perfused suits. Measurements included heart rate (HR), cardiac output (Q˙c; acetylene rebreathing technique), central venous pressure (CVP), blood pressures, forearm blood flow (venous occlusion plethysmography), splanchnic and renal blood flows (indocyanine green and p-aminohippurate clearance), and esophageal and mean skin temperatures. In response to tilting in the thermoneutral condition, CVP and stroke volume decreased to a greater extent in the young men, but HR increased more, such that the fall in Q˙cwas similar between the two groups in the upright posture. The rise in splanchnic vascular resistance (SVR) was greater in the older men, but the young men increased forearm vascular resistance (FVR) to a greater extent than the older men. The fall inQ˙cduring combined heat stress and tilting was greater in the young compared with older men. Only four of the young men versus six of the older men were able to finish the second tilt without becoming presyncopal. In summary, the older men relied on a greater increase in SVR to compensate for a reduced ability to constrict the skin and muscle circulations (as determined by changes in FVR) during head-up tilting.
Drinking and blood pressure during sodium depletion or ANG II infusion in chronic cholestatic rats
Authors: Fitts Douglas A. , Lane Jeannine R. , Starbuck Elizabeth M. , Li Chi-Pei
Published: December 2017

After a chronic ligation of the common bile duct (BDL), Long-Evans rats are hypotensive and have elevated saline intake during both sodium-depleted and nondepleted conditions. We tested whether BDL rats have exaggerated hypotension during sodium depletion or an elevated dipsogenic response to angiotensin II (ANG II) that might help to explain the saline intake. After 4 wk of BDL, rats were hypotensive at baseline and developed exaggerated hypotension during acute furosemide-induced diuresis. Without saline to drink, BDL rats increased water intake during depletion equal to sham-ligated rats. However, with saline solution available at 22 h after sodium depletion, the BDL rats drank more water and saline than did sham-ligated rats. This rapid intake temporarily increased their mean arterial pressure to equal that of sham-ligated rats. Intravenous infusion of ANG II induced equal drinking responses despite reduced pressor responses in the BDL rats relative to sham-ligated rats during both ad libitum and sodium-depleted conditions. Thus BDL rats have exaggerated hypotension during diuresis, and their hypotension is corrected by drinking an exaggerated volume of saline, but they do not have an increased drinking response to ANG II.
Contribution of lungs to desipramine-induced changes in whole body catecholamine kinetics in newborn lambs
Authors: Smolich Joseph J. , Cox Helen S. , Esler Murray D.
Published: December 2017

To characterize pulmonary and total body norepinephrine and epinephrine kinetics in the immediate newborn period, the effects of desipramine were studied in six fetal lambs chronically instrumented at 133–134 days gestation (term 147 days) and delivered 1 wk later by cesarean section under spinal anesthesia. Norepinephrine and epinephrine kinetics were determined with isotope dilution methodology 4 h after birth and repeated 30 min after desipramine (2 mg/kg iv). At baseline, the lungs accounted for 35 ± 10 and 47 ± 13% of whole body norepinephrine clearance (93 ± 8 ml ⋅ min−1 ⋅ kg−1) and spillover (188 ± 29 ng ⋅ min−1 ⋅ kg−1) and 15 ± 2 and 19 ± 7% of whole body epinephrine clearance (82 ± 4 ml ⋅ min−1 ⋅ kg−1) and release (22.7 ± 2.7 ng ⋅ min−1 ⋅ kg−1), respectively. Desipramine decreased pulmonary norepinephrine and epinephrine clearance and spillover to near-zero levels, whereas whole body norepinephrine clearance fell by 51 ± 3% ( P < 0.001), norepinephrine spillover by 54 ± 6% ( P < 0.005), epinephrine clearance by 30 ± 6% ( P < 0.01), and epinephrine spillover by 34 ± 11% ( P < 0.05). These results indicate that, in the immediate newborn period, pulmonary removal and release of norepinephrine and epinephrine is mediated by a desipramine-sensitive process that accounts for a major portion of associated reductions in whole body norepinephrine and epinephrine clearance and release.
Thirst and salt appetite elicited by hypovolemia in rats with chronic lesions of the nucleus of the solitary tract
Authors: Schreihofer Ann M. , Anderson Brett K. , Schiltz Jennifer C. , Xu Ling , Sved Alan F. , Stricker Edward M.
Published: December 2017

Cardiac vagal afferents terminating in the nucleus of the solitary tract (NTS) are believed to participate in stimulating neurohypophysial secretion of vasopressin as well as increased ingestion of water and NaCl solution in response to decreased blood volume. However, we recently reported that chronic lesions of NTS, which eliminate neural input from cardiac and arterial baroreceptors, do not impair hypovolemia-induced vasopressin secretion in rats. In the present investigation we sought to determine whether those sensory signals were necessary for hypovolemia-induced thirst and salt appetite. Rats with chronic lesions of the NTS increased consumption of water and NaCl solution normally when plasma volume was reduced isosmotically by subcutaneous injection of polyethylene glycol solution. These results were obtained whether rats were allowed to drink water or 0.15 M NaCl in one-bottle tests or water and 0.5 M NaCl in two-bottle tests. The induction of thirst and salt appetite by hypovolemia despite the apparent loss of neural input to the brain from cardiac volume-sensitive receptors indicates that other signals generated by plasma volume deficits can stimulate these behavioral responses in rats.
Ca2+-induced Ca2+release involved in positive inotropic effect mediated by CGRP in ventricular myocytes
Authors: Huang Ming-He , Knight Paul R. , Izzo Joseph L.
Published: December 2017

To investigate the effects and mechanisms of calcitonin gene-related peptide (CGRP) on ventricular contractility, ventricular myocytes isolated from adult rat and mouse hearts were exposed to CGRP. Myocyte contractility was assessed by a video edge motion detector, and the intracellular [Ca2+] transients were measured by a spectroflurophotometer in fura 2-loaded myocytes. CGRP exerted a potent concentration-dependent (10 pM–10 nM, EC50= 44.1 pM) positive inotropism on rat ventricular myocytes. CGRP (1 nM) increased cell shortening during contraction by 140 ± 40% above baselines and increased maximum velocity of contraction and relaxation by 98 and 106%, respectively. CGRP failed to produce any response in the presence of the CGRP1receptor antagonist. CGRP induced similar inotropic response in mouse ventricular myocytes. CGRP increased the amplitude of [Ca2+] transients of ventricular myocytes by 120 ± 25% above baseline and shortened the time of half-maximum myoplasmic Ca2+clearance by 30 ± 5%. Increase in intracellular Ca2+mobilization by CGRP was dependent on Ca2+influx through the activation of the L-type Ca2+channel, because nifedipine blocked the CGRP-induced increase in [Ca2+] transients. Furthermore, CGRP failed to increase [Ca2+] transients after the inhibition of protein kinase A in ventricular myocytes. These data indicate that stimulation of mammalian ventricular myocardial CGRP1receptors enhances [Ca2+] transients through the activation of protein kinase A, which in turn activates voltage-dependent L-type Ca2+channels. These events lead to Ca2+-induced intracellular Ca2+release and enhanced myocyte contraction and facilitated relaxation.
Role of nitric oxide and cGMP in human septic serum-induced depression of cardiac myocyte contractility
Authors: Kumar Anand , Brar Rupinder , Wang Peter , Dee Linda , Skorupa Greg , Khadour Fadi , Schulz Richard , Parrillo Joseph E.
Published: December 2017

Previous studies have demonstrated the existence of a circulating myocardial depressant substance during human septic shock. We have recently identified this substance as a synergistic combination of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). This study utilized an in vitro cardiac myocyte assay to evaluate the potential mechanistic role of nitric oxide (NO) and cGMP in depression of myocyte contractility induced by TNF-α, IL-1β, TNF-α + IL-1β (at low concentrations), and human septic shock serum (HSS). TNF-α, IL-1β, TNF-α + IL-1β, and each of 5 sera from patients with acute septic shock caused depression of both maximum extent and peak velocity of cardiac myocyte shortening and an increase in intracellular cGMP concentration during 30 min of exposure (minimum P < 0.01). NO synthetase (NOS) and guanylate cyclase inhibitors such as N-methyl-l-arginine (l-NMA) and methylene blue prevented these effects; an excess ofl-arginine withl-NMA restored them (minimum P < 0.01). In contrast,d-arginine failed to reestablish cytokine-induced myocyte depression and cGMP accumulation prevented byl-NMA. Exposure of myocytes to TNF-α, IL-1β, or TNF-α + IL-1β produced a concentration-dependent increase in intracellular cGMP that paralleled the depression of cardiac myocyte contractility (minimum P < 0.001). In addition, TNF-α, IL-1β, TNF-α + IL-1β, or HSS application to cardiac myocytes resulted in increased NO gas generation, which was inhibited byl-NMA (minimum P < 0.01). Furthermore, unstimulated cardiac myocytes were shown to harbor constitutive but not inducible NOS activity. These data suggest that the sequential generation of NO by a constitutive NOS and cGMP by guanylate cyclase represents an important mechanism of cardiac myocyte depression by TNF-α, IL-1β, TNF-α + IL-1β, and the myocardial depressant substance(s) of septic shock.
Induction of endogenous tumor necrosis factor-α: suppression of centrally stimulated gastric motility
Authors: Hermann Gerlinda E. , Tovar C. Amy , Rogers Richard C.
Published: December 2017

Gastric stasis is frequently seen in conjunction with critical infectious illness, chronic inflammatory disorders, radiation sickness, and carcinogenesis. These conditions are associated with elevated circulating levels of the cytokine tumor necrosis factor-α (TNF-α). The present studies examined the relationship between endogenously produced TNF-α and the central neural mechanisms that augment gastric motility. Systemic lipopolysaccharide (LPS) was employed to induce TNF-α production in thiobutabarbital-anesthetized rats. Sixty minutes after intravenous LPS injection, gastric motility could not be stimulated by a potent centrally acting gastrokinetic stimulant, thyrotropin-releasing hormone (TRH). This failure to elicit gastric motility via central mechanisms coincided with high circulating levels of TNF-α. However, intravenous injections of bethanecol, a peripherally acting cholinergic agonist with direct gastrokinetic effects, were still able to elicit normal increases in gastric motility in the presence of TNF-α and LPS. Therefore, the inability to stimulate gastric motility via central TRH could not be attributed to the direct inhibitory effects of either LPS or TNF-α on the stomach. If the production of endogenous TNF-α was suppressed via the use of urethan as the anesthetic agent, then intravenous injections of LPS were no longer effective in suppressing gastric motility. Thus these effects on gastric motility are not directly attributable to LPS nor are they due to direct effects on the gastric smooth muscle. Our previous study demonstrated that microinjection of femtomole quantities of TNF-α in the brain stem dorsal vagal complex (DVC) can modulate gastric motility. This central TNF-α effect on gastric motility was dose dependent and required an intact vagal efferent pathway. The results from these two studies suggest that systemically produced TNF-α may gain access to the DVC to modulate gastric function.
Chronic hypercapnia resets CO2 sensitivity of avian intrapulmonary chemoreceptors
Authors: Bebout D. E. , Hempleman S. C.
Published: December 2017

Avian intrapulmonary chemoreceptors (IPC) are vagal sensory neurons that participate in the control of breathing. IPC action potential frequency is inversely proportional to [Formula: see text], but it is unclear whether low [Formula: see text] or high pH is the immediate stimulus for signal transduction in IPC. To address this question, comparisons were made between single cell neural responses of 34 IPC recorded in 6 anesthetized ducks ( Anas platyrhynchos) acclimatized 12 days to 7.5% inspired CO2 and 22 IPC recorded in 9 normal anesthetized ducks. We hypothesized that if respiratory-linked pH changes determine IPC activity, action potential frequency as a function of inspiratory[Formula: see text]([Formula: see text]) should be greater after acclimatization due to metabolic acid-base compensation and higher pH. Conversely, if[Formula: see text] alone determines IPC discharge, action potential frequency vs.[Formula: see text] should be unchanged by acclimatization. Results indicate that after acclimatization ventilation was depressed at 28 and 42 Torr[Formula: see text]( P < 0.05) and mean plasma pH at 40 Torr [Formula: see text] increased from 7.38 ± 0.03 to 7.56 ± 0.02 ( P < 0.05), indicating significant metabolic acid-base compensation and[Formula: see text] retention. Mean IPC discharge rate was elevated by CO2acclimatization at all [Formula: see text] studied. In acclimatized vs. normal animals, regression analysis of IPC discharge as a function of[Formula: see text] showed increased mean intercepts of 81.1 ± 4.0 vs. 48.4 ± 3.6 impulses/s ( P < 0.05) and increased mean slopes of −19.0 ± 1.0 vs. −12.0 ± 1.1 impulses ⋅ s−1 ⋅ [Formula: see text] −1( P < 0.05). Results indicate that IPC response to CO2 is mediated by H+ from CO2 hydration and not by CO2 directly.
CCK-A receptor antagonists have selective effects on nutrient-induced food intake suppression in rats
Authors: Trigazis L. , Vaccarino F. J. , Greenwood C. E. , Anderson G. H.
Published: December 2017

To provide additional support to the hypothesis that only dietary protein (Pro; chicken egg albumin) and not amino acids (AA; patterned after albumin), carbohydrates (CHO; cornstarch), or fats (Fat; corn oil) produces a satiating effect via CCK receptors, two CCK-A receptor antagonists (PD-140,548 and devazepide) were coadministered with each nutrient. Given alone [4 ml intragastrically (ig)] Pro (1.0 g), AA (1.0 g), CHO (1.4 g), and Fat (2.4 g) suppressed ( P< 0.05) food intake on average during the first 2 h of feeding by 1.4 (36%), 1.5 (48%), 1.0 (33%), and 1.2 g (41%), respectively. Devazepide (0.5 mg/kg) and PD-140,548 (1.0 mg/kg) given alone increased food intake during 0–2 h by 0.7 g (18%) and during 0–1 h by 0.5 g (15%), respectively. When coadministered with PD-140,548 (1.0 mg/kg ip), the suppression of food intake caused by Pro was modulated during 0–2 h by 57% (Pro × drug interaction, P < 0.05), but AA-, CHO-, and Fat-induced suppression of feeding was not affected (nutrient × drug interaction, P > 0.05). Devazepide (0.5 mg/kg ip) did not modulate AA-, CHO-, and Fat-induced food intake suppression during any time period (nutrient × drug interaction, P > 0.05). These studies provide additional evidence that CCK-A receptors play a role in Pro (albumin) but not AA-, CHO (cornstarch)-, or Fat (corn oil)-induced food intake suppression in rats.
Oxygen binding and its allosteric control in hemoglobin of the pulmonate snail,Biomphalaria glabrata
Authors: Bugge Jon , Weber Roy E.
Published: December 2017

Pulmonate snails that experience extreme variations in gas tensions and temperatures possess extracellular, high-molecular mass (∼1.7 × 106Da) hemoglobins (Hbs) that are little known as regards oxygenation and allosteric characteristics. Biomphalaria glabrata hemolymph exhibits a high O2affinity (half-saturation O2tension = 6.1 mmHg; pH 7.7, 25°C), pronounced Bohr effect (Bohr factor = −0.5), and pH-dependent cooperativity (Hill’s cooperativity coefficient at half-saturation = 1.1–2.0). Divalent cations increase O2affinity, Ca2+exerting greater effect than Mg2+. Analyses in terms of the Monod-Wyman-Changeux model indicate novel O2affinity control mechanisms. In contrast to vertebrate Hb, where organic phosphates and protons lower affinity via decreased O2association equilibrium constant of Hb in low-affinity state ( KT), and to extracellular annelid Hbs, where protons and cations primarily modulate O2association equilibrium constant of Hb in high-affinity state ( KR), in B. glabrata Hb, the Bohr effect is mediated predominantly via KRand the cation effect via KT, reflecting preferential, oxygenation-linked proton binding to oxygenated Hb and cation binding to deoxygenated Hb. CO2has no specific (pH independent) effect. Nonlinear van’t Hoff plots show temperature dependence of the overall heats of oxygenation, indicating oxy-deoxy heat capacity differences. The findings are related to possible physiological significance in pond habitats.
Cholecystokinin and serotonin receptors in the regulation of fat-induced satiety in rats
Authors: Burton-Freeman Britt , Gietzen Dorothy W. , Schneeman Barbara O.
Published: December 2017

The present study investigated the relationship between endogenous CCK and serotonin (5-HT) in fat-induced satiety. Male Wistar rats with duodenal cannulas were adapted to eating 6 h/day along with receiving an infusion of saline or one of two isocaloric solutions (10 ml, 1 kcal/ml, 0.45 ml/min) varying in fat and carbohydrate content (20 or 80% energy from fat). Rats were infused 10 min after food presentation. The satiation/satiety response was determined from measures of meal size (MS), intermeal interval (IMI), and total food intake (TFI). Infusion with either fat solution reduced MS compared with saline; however, the 80% fat infusate reduced TFI and lengthened the IMI compared with saline and the 20% fat infusate. CCK and 5-HT involvement in fat-induced satiety was investigated by preceding the 80% fat infusate with CCK and/or 5-HT3 receptor antagonists Devazepide (Dev) and Tropisetron (Trop). A CCK releaser, trypsin inhibitor (TI), was added to the 20% fat infusate to enhance satiety. Pretreatment with Dev or Trop alone attenuated the inhibitory effects of the 80% solution on IMI, whereas reversal of the inhibitory effects on MS and TFI were sensitive only to Dev at the doses provided. Both antagonists together completely blocked the satiating effects of the 80% fat infusate on all feeding variables measured. Addition of TI to the 20% fat infusate lengthened the IMI but did not affect MS or TFI. These results provide evidence for the participation of both endogenous CCK and 5-HT in the satiety response to fat in the intestine.
Intracavernous pressure during erection in rats: an integrative approach based on telemetric recording
Authors: Bernabé Jacques , Rampin Olivier , Sachs Benjamin D. , Giuliano François
Published: December 2017

To better understand the similarities and differences in the neural control of penile erection occurring in different contexts, we recorded intracavernous pressure (ICP) in conscious rats using a miniaturized telemetric device. ICP changes during reflexive, noncontact, and apomorphine-induced erections were characterized by a plateau increase surmounted by peaks. Plateaus were also elicited by cavernous nerve stimulation in anesthetized rats, suggesting that the cavernous nerve represents the final common proerectile autonomic pathway in these contexts and that it responds similarly to information originating in the periphery or in supraspinal nuclei. During reflexive, noncontact, and apomorphine-induced erections, activation of spinal autonomic nuclei, considered the spinal generators of erection, would take place first, representing a prerequisite for the occurrence of peaks. Suprasystolic peaks would result from the addition of pudendal motoneuron activity. In contrast, only peaks were recorded during copulation. In this context, the convergence of peripheral and supraspinal information apparently elicits the best temporal arrangement of autonomic and somatic outflows, reflecting a highly organized and integrated spinal activity.
Sepsis is associated with increased ubiquitinconjugating enzyme E214k mRNA in skeletal muscle
Authors: Hobler Scott C. , Wang Jing Jing , Williams Arthur B. , Melandri Francesco , Sun Xiaoyan , Fischer Josef E. , Hasselgren Per-Olof
Published: December 2017

Previous studies provided evidence that sepsis is associated with increased ubiquitin-proteasome-dependent protein breakdown in skeletal muscle. The 14-kDa ubiquitin-conjugating enzyme (E214k) has been proposed to be a key regulator of the ubiquitin proteolytic pathway. We tested the hypothesis that E214k message and protein levels are increased in skeletal muscle during sepsis. Sepsis was induced in rats by cecal ligation and puncture (CLP). Control rats were sham operated. E214k mRNA and protein levels were quantitated after Northern and Western blot analysis, respectively, 16 h after CLP or sham operation. Sepsis resulted in a 70% increase in the 1.2-kb E214k transcript in the fast-twitch extensor digitorum longus muscle, whereas no changes were seen in the slow-twitch soleus muscle. E214k protein levels were not influenced by sepsis in any of the muscles studied. Although the changes in the expression of the E214k 1.2-kb transcript paralleled the differential effect of sepsis on protein breakdown in fast- and slow-twitch muscle, the potential role of E214k in the regulation of sepsis-induced muscle proteolysis needs to be interpreted with caution, because the results demonstrated that increased message levels were not associated with increased E214kprotein levels.
Centrally mediated effect of 17β-estradiol on parasympathetic tone in male rats
Authors: Saleh Tarek M. , Connell Barry J.
Published: December 2017

The following experiments were conducted to determine if peripherally administered estrogen has an effect on central autonomic tone and whether this change in tone results in an alteration in cardiovascular reflex control. Male Sprague-Dawley rats were anesthetized with thiobutabarbitol sodium (50 mg/kg) and instrumented to record blood pressure, heart rate, and vagal parasympathetic or renal sympathetic efferent nerve activity. Additional rats were instrumented to test the sensitivity of the cardiac baroreflex using intravenous injections of phenylephrine hydrochloride (0.025, 0.05, 0.1 mg/kg) or sodium nitroprusside (0.0025, 0.005, 0.01 mg/kg) and plotting the cardiovascular responses. Intravenous injection of estrogen (10−4, 10−2, and 10−1 mg/kg) produced a significant increase in vagal efferent activity and in baroreflex sensitivity. The bilateral microinjection of an estrogen receptor antagonist, ICI-182,780 (1 pM, 50 nl/side) into the nucleus ambiguus blocked both the estrogen-induced increase in vagal efferent activity and baroreflex sensitivity. These results demonstrate that in male rats estrogen acts centrally to enhance baroreflex sensitivity by increasing parasympathetic efferent tone.
Na+-K+-ATPase and Na+/Ca2+exchange activities in gills of hyperregulatingCarcinus maenas
Authors: Lucu Čedomil , Flik Gert
Published: December 2017

Na+-K+-ATPase and Na+/Ca2+exchange activities were studied in gills of Carcinus maenas in seawater (SW) and after transfer to dilute seawater (DSW). Carcinushyperregulates its hemolymph osmolarity through active uptake of Na+, Cl−, and Ca2+. In DSW total Na+-K+-ATPase activity in posterior gills quadrupled; Na+/Ca2+exchange specific activity was unaffected, and total activity increased 1.67-fold. Short-circuit current ( Isc) in voltage-clamped posterior gill hemilamellae was −181 μA/cm2in SW and −290 μA/cm2in DSW and up to 90% ouabain sensitive; conductivity was similar in SW or DSW (42 and 46 mS/cm2, respectively) and representative of a leaky epithelium. The new steady state of hemolymph osmolarity 24 h after DSW transfer was preceded, already 3 h after transfer, by increased Na+-K+-ATPase but not Na+/Ca2+exchange activity. Western blot analysis indicated that the amount of Na+-K+-ATPase protein had increased 2.1-fold in crabs acclimated 3 wk to DSW; however, 4 h after DSW transfer no difference in the amount of Na+-K+-ATPase protein was observed. After DSW transfer branchial cAMP content decreased. A negative correlation between branchial Na+-K+-ATPase activity and cAMP content points to rapid regulation of Na+-K+-ATPase through cAMP-dependent protein kinase A activity. Ca2+transport may depend on the high-capacity Na+/Ca2+exchanger coupled to the versatile sodium pump.
Circadian blood pressure and heart rate rhythms in mice
Authors: Li Ping , Sur Steven H. , Mistlberger Ralph E. , Morris Mariana
Published: December 2017

The circadian pattern of mean arterial pressure (MAP) and heart rate (HR) was measured in C57BL mice with carotid arterial catheters. Cardiovascular parameters were recorded continuously with a computerized monitoring system at a sampling rate of 100 Hz. The tethered animals were healthy, showing stabilized drinking and eating patterns within 2 days of surgery and little loss of body weight. Analysis of the 24-h pattern of MAP and HR was conducted using data from 3–6 consecutive days of recording. A daily rhythm of MAP was evident in all mice, with group mean dark and light values of 101.4 ± 7.3 and 93.1 ± 2.9 mmHg, respectively. The group mean waveform was bimodal, with peak values evident early and late in the dark period, and a trough during the middle of the light period. The phase of maximum and minimum values showed low within-group variance. Mean heart rate was greater at night than during the day (561.9 ± 22.7 vs. 530.3 ± 22.3 beats/min). Peak values generally occurred at dark onset, and minimum values during the middle of both the dark and the light periods. We conclude that it is possible to perform measurements of circadian cardiovascular parameters in the mouse, providing new avenues for the investigation of genetic models.
O2consumption and heart rate in developing zebrafish (Danio rerio): influence of temperature and ambient O2
Authors: Barrionuevo W. R. , Burggren W. W.
Published: December 2017

Body mass, length, oxygen consumption (M˙o2) and heart rate ( fH) were measured in “embryos” (prior to hatching), “larvae” ( days 10–20), “juveniles” ( days 30–70 in 10-day intervals), and “adults” ( day 100) of the zebrafish Danio rerio. Fish were chronically reared at either 25, 28, or 31°C and then acutely exposed to hypoxia at different developmental stages. We hypothesized that at any given rearing and measurement temperature, D. rerio would maintainM˙o2at lower ambient [Formula: see text] [i.e., have a lower critical partial pressure (Pcrit)] as development progressed and that at any given developmental stage individuals reared and measured at higher temperatures would show a more pronounced hypoxic bradycardia.M˙o2in normoxic fish at 28°C peaked at ∼40 μmol ⋅ g−1⋅ h−1at day 10, thereafter falling to 4–5 μmol ⋅ g−1⋅ h−1at day 100. The Q10forM˙o2was 4–5 in embryos, falling to 2–3 from day 10 to day 60 and rising again to 4–5 at day 100. Pcritat 28°C was ∼80 mmHg in embryos but decreased sharply to 20 mmHg at 100 days, supporting the hypothesis that more mature fish would be better able to oxygen regulate to lower ambient [Formula: see text] levels. Pcritincreased sharply with measurement temperature. Heart rate ( fH) at 28°C increased from about 125 beats/min in embryos to a peak of ∼175 beats/min at days 10–30and then fell to ∼130 beats/min by day 100. Unlike forM˙o2, the Q10for fHwas more constant at 1.2–2.5 throughout development. Hypoxic exposure at any temperature had no effect on fHuntil ∼ day 30, after which time a hypoxic bradycardia was evident. As evident forM˙o2, the bradycardia in older larvae was more profound at higher temperatures. On the assumption that bradycardia is indicative of hypoxic stress, the increasing prevalence of a hypoxic bradycardia in older, warmer individuals supports the hypothesis that increasing hypoxic susceptibility with development would be exacerbated by increasing temperature. Collectively, these data indicate that the ability to regulateM˙o2and fHin response to the compounding demands of increased temperature and/or decreased oxygen availability first develops after ∼20 days in D. rerio and, thereafter, the ability to maintainM˙o2in the face of ambient hypoxia progressively builds through to adulthood. Additionally, the temperature responses of metabolism and heart rate differ substantially at different phases of development, suggesting a loose coupling between the respiratory and cardiovascular systems, at least early in development.
Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups
Authors: DiBona Gerald F. , Sawin Linda L.
Published: December 2017

To examine the effect of activation of a unique population of renal sympathetic nerve fibers on renal blood flow (RBF) dynamics, anesthetized rats were instrumented with a renal sympathetic nerve activity (RSNA) recording electrode and an electromagnetic flow probe on the ipsilateral renal artery. Peripheral thermal receptor stimulation (external heat) was used to activate a unique population of renal sympathetic nerve fibers and to increase total RSNA. Total RSNA was reflexly increased to the same degree with somatic receptor stimulation (tail compression). Arterial pressure and heart rate were increased by both stimuli. Total RSNA was increased to the same degree by both stimuli but external heat produced a greater renal vasoconstrictor response than tail compression. Whereas both stimuli increased spectral density power of RSNA at both cardiac and respiratory frequencies, modulation of RBF variability by fluctuations of RSNA was small at these frequencies, with values for the normalized transfer gain being ∼0.1 at >0.5 Hz. During tail compression coherent oscillations of RSNA and RBF were found at 0.3–0.4 Hz with normalized transfer gain of 0.33 ± 0.02. During external heat coherent oscillations of RSNA and RBF were found at both 0.2 and 0.3–0.4 Hz with normalized transfer gains of 0.63 ± 0.05 at 0.2 Hz and 0.53 ± 0.04 to 0.36 ± 0.02 at 0.3–0.4 Hz. Renal denervation eliminated the oscillations in RBF at both 0.2 and 0.3–0.4 Hz. These findings indicate that despite similar increases in total RSNA, external heat results in a greater renal vasoconstrictor response than tail compression due to the activation of a unique population of renal sympathetic nerve fibers with different frequency-response characteristics of the renal vasculature.
Heat acclimation induces changes in cardiac mechanical performance: the role of thyroid hormone
Authors: Mirit Eynan , Palmon Aharon , Hasin Yonathan , Horowitz Michal
Published: December 2017

The involvement of reduced thyroxine level in the emergence of heat acclimation-induced negative lusitropic effect was examined. Experiments were carried out on 1) control rat hearts maintained at 24 ± 1°C (C); 2) rat hearts acclimated at 34°C for 1 mo (AC); 3) AC-euthyroid rat hearts, via administration of thyroxine in the drinking water (AT); and 4) hypothyroid rat hearts, maintained at 24 ± 1°C, via administration of thiouracil in the drinking water (CP). Systolic pressure and velocities of contraction (dP/d t ⋅ P) and relaxation (−dP/d t ⋅ P) were measured using the Langendorff perfusion system. The steady-state levels of Ca2+-ATPase and phospholamban mRNAs and the expression of the encoded proteins Ca2+-ATPase (SERCA) and phospholamban (PLB) were measured, using semi-quantitative RT-PCR and Western immunoblotting, respectively. Rat thyroxine levels were measured using RIA. Heat acclimation, which brought about a reduced thyroxine level, led to downregulation of Ca2+-ATPase mRNA expression and translation and upregulation of phospholamban mRNA and PLB. Consequently, the PLB-to-SERCA ratio (PLB/SERCA) of the AC hearts showed a significant increase. These changes, as well as the greater pressure generation and the reduced dP/d t ⋅ P and −dP/d t ⋅ P observed in AC hearts were blunted in the AT hearts. Our data suggest that sustained heat acclimation-induced low thyroxine level has a decisive effect on the contractile machinery of the AC heart. Elevated PLB/SERCA apparently explains the negative lusitropic effect observed in these hearts.
Regulation of fiber size, oxidative potential, and capillarization in human muscle by resistance exercise
Authors: Green H. , Goreham C. , Ouyang J. , Ball-Burnett M. , Ranney D.
Published: December 2017

To examine the hypothesis that increases in fiber cross-sectional area mediated by high-resistance training (HRT) would result in a decrease in fiber capillarization and oxidative potential, regardless of fiber type, we studied six untrained males (maximum oxygen consumption, 45.6 ± 2.3 ml ⋅ kg−1 ⋅ min−1; mean ± SE) participating in a 12-wk program designed to produce a progressive hypertrophy of the quadriceps muscle. The training sessions, which were conducted 3 times/wk, consisted of three sets of three exercises, each performed for 6–8 repetitions maximum (RM). Measurements of fiber-type distribution obtained from tissue extracted from the vastus lateralis at 0, 4, 7, and 12 wk indicated reductions ( P < 0.05) in type IIB fibers (15.1 ± 2.1% vs. 7.2 ± 1.3%) by 4 wk in the absence of changes in the other fiber types (types I, IIA, and IIAB). Training culminated in a 17% increase ( P < 0.05) in cross-sectional area by 12 wk with initial increases observed at 4 wk. The increase was independent of fiber type-specific changes. The number of capillaries in contact with each fiber type increased by 12 wk, whereas capillary contacts-to-fiber area ratios remained unchanged. In a defined cross-sectional field, HRT also increased the capillaries per fiber at 12 wk. Training failed to alter cellular oxidative potential, as measured by succinic dehydrogenase (SDH) activity, regardless of fiber type and training duration. It is concluded that modest hypertrophy induced by HRT does not compromise cellular tissue capillarization and oxidative potential regardless of fiber type.
Measurement of gastric emptying during and between meal intake in free-feeding Lewis rats
Authors: van der Velde P. , Koslowsky I. , Koopmans H. S.
Published: December 2017

A new scintigraphic measurement technique is described that allows accurate assessment of gastric emptying in between as well as during a number of successive meals. Measurements were made every minute of food intake, gastric nutrient filling, and gastric emptying over a 6 h, 40 min period in conscious, free-feeding, loosely restrained rats. Before receiving access to the food, the animals had been deprived for a period of 31 h. Over the full duration of the experiment, an average rate of gastric emptying of 2.46 ± 0.18 (SE) kcal/h was established. During most meals, however, the gastric emptying rate was increased so that an average of 26.9 ± 2.7% of the ingested calories was emptied while the animals were feeding, with an average emptying rate of 0.15 ± 0.014 kcal/min or 8.88 ± 0.84 kcal/h. This transient increase in the rate of gastric emptying was followed by a subsequent slowing of gastric emptying after meal termination; in the 10-min postmeal interval, an average emptying rate of 0.96 ± 0.12 kcal/h was found. Despite these fluctuations during and immediately after meals, a relatively constant rate of caloric emptying is maintained over longer periods. There were no differences between the emptying rate during the first meal when the gastrointestinal tract was still empty, compared with later meals when the gastrointestinal tract had been filled with food. The emptying rate during the 10-min postmeal interval, however, was significantly reduced during later meals. The results suggest that gastric emptying is controlled by different mechanisms during and after the ingestion of food and that these mechanisms remain in effect at various degrees of gastrointestinal filling.
Elevation of basolateral K+induces K+ secretion by apical maxi K+ channels inAmbystoma collecting tubule
Authors: Stoner Larry C. , Viggiano Susan C.
Published: December 2017

We previously reported that exposure of aquatic-phase Ambystoma tigrinum to a solution containing 50 mM K+(K+ adaptation) caused a nearly 10-fold increase in the number of detectable maxi K+ channels on the apical membrane of their initial collecting tubules. In apparent contradiction to the notion that maxi K+ channels contribute to K+ secretion, these channels were not routinely active at the resting membrane potential (0 mV voltage clamp). To test the possibility that hyperkalemia yields maxi K+ channels that are secreting K+ (i.e., active at 0 mV), we patch-clamped the apical membranes of initial collecting tubules under conditions of elevated basolateral K+ (15 mM). Seven patches containing maxi K+ channels were studied. Six of the seven patches showed maxi K+ channel activity when voltage was clamped at 0 mV. Open probability and unitary current averaged 0.059 ± 0.016 and 1.65 ± 0.50 pA, respectively. This activity, together with the high density of channels observed (1.06 channels/μm2), indicates that after K+ adaptation, maxi K+ channels contribute to the ability of the late distal nephron of amphibians to secrete K+.
Molecular characterization of an elasmobranch urea transporter
Authors: Smith Craig P. , Wright Patricia A.
Published: December 2017

Marine elasmobranch fishes retain relatively high levels of urea to balance the osmotic stress of living in seawater. To maintain osmotic balance and reduce the energetic costs of making urea, it is important for these animals to minimize urea excretion to the environment. We have isolated a novel 2.2-kb cDNA from Squalus acanthias (spiny dogfish shark) kidney encoding a 380-amino acid hydrophobic protein (ShUT) with 66% identity to the rat facilitated urea transporter protein UT-A2. Injection of ShUT cRNA into Xenopusoocytes induced a 10-fold increase in14C-labeled urea uptake, inhibitable by phloretin (0.35 mM). ShUT mRNA is expressed in kidney and brain. Related mRNA species are found in liver, blood, kidney, gill, intestine, muscle, and rectal gland. This is the first facilitated urea transporter to be identified in a marine fish. We propose that the ShUT protein is involved in urea reabsorption by the renal tubules of the dogfish shark, which in turn minimizes urea loss in the urine.
Expression of Na+-d-glucose cotransporter in brush-border membrane of the chicken intestine
Authors: Garriga Carles , Rovira Nativitat , Moretó Miquel , Planas Joana M.
Published: December 2017

We have studied the expression of Na+-d-glucose cotransporter in brush-border membrane vesicles (BBMVs) of chicken enterocytes to correlate the changes in the apical Na+-dependent transport with the changes in the amounts of transporter determined by Western blot analysis. Two different rabbit polyclonal antibodies were used simultaneously. The antibody raised against amino acids 564–575 of the deduced amino acid sequence of rabbit intestinal SGLT-1 ( antibody 1) specifically detects a single 75-kDa band in the three segments, and this band disappeared when the antibody was preabsorbed with the antigenic peptide. The antibody raised against the synthetic peptide corresponding to amino acids 402–420 of the same protein ( antibody 2) only reacts with jejunal and ileal samples, but no signal is found in BBMVs of rectum. Only when antibody 1 was used was there a linear correlation between the maximal transport rates of hexoses in BBMVs and the relative protein amounts determined by Western blot. These results indicate that the Na+-d-glucose cotransport in the jejunum, the ileum, and the rectum of chickens is due to an SGLT-1 type protein.
Effect of prostanoids and their precursors on the aggregation of rainbow trout thrombocytes
Authors: Hill D. J. , Hallett M. B. , Rowley A. F.
Published: December 2017

The role of prostanoids and their precursor fatty acids in the aggregatory response of thrombocytes (platelet equivalents of fish) from the rainbow trout, Oncorhynchus mykiss, was studied. Aggregation of these cells was induced by the thromboxane mimetic U-46619 or arachidonic acid (AA) in the presence of human or trout fibrinogen. The production of TXB2/3by thrombocytes in response to stimulation with AA was inhibited by aspirin, ibuprofen, and indomethacin. However, thrombocyte aggregation in response to AA stimulation was not significantly altered by these agents at the concentrations tested (10–100 μM), with the exception of indomethacin at 20 and 40 μM. Effects on cytosolic calcium concentration have been suggested as an alternative mechanism for the inhibitory action of indomethacin on human platelet aggregation. The present study, however, failed to identify this as a mechanism for the inhibition of U-46619-induced trout thrombocyte aggregation by indomethacin. The polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid both exhibited an inhibitory effect on U-46619-induced thrombocyte aggregation similar to that observed with mammalian platelets. Unlike the case in mammalian hemostasis, prostacyclin inhibited thrombocyte aggregation only at high concentrations (>5 μM). Prostaglandin E2, however, inhibited thrombocyte aggregation at much lower concentrations (>0.01 μM), suggesting that it may be the major inhibitory eicosanoid in trout.
Effect of individual or combined ablation of the nuclear groups of the lamina terminalis on water drinking in sheep
Authors: McKinley M. J. , Mathai M. L. , Pennington G. , Rundgren M. , Vivas L.
Published: December 2017

The subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), and median preoptic nucleus (MnPO) were ablated either individually or in various combinations, and the effects on drinking induced by either intravenous infusion of hypertonic 4 M NaCl (1.3 ml/min for 30 min) or water deprivation for 48 h were studied. Ablation of either the OVLT or SFO alone did not affect drinking in response to intravenous 4 M NaCl, although combined ablation of these two circumventricular organs substantially reduced but did not abolish such drinking. Ablation of the MnPO or MnPO and SFO together also substantially reduced, but did not abolish, drinking in response to intravenous hypertonic NaCl. Only near-total destruction of the lamina terminalis (OVLT, MnPO, and part or all of the SFO) abolished acute osmotically induced drinking. The large lesions also reduced drinking after water deprivation, whereas none of the other lesions significantly affected such drinking. None of these lesions altered feeding. The results show that all parts of the lamina terminalis play a role in the drinking induced by acute increases in plasma tonicity. The lamina terminalis appears to play a less crucial role in the drinking response after water deprivation than for the drinking response to acute intravenous infusion of hypertonic saline.
Perfusion of the human finger during cold-induced vasodilatation
Authors: Bergersen T. K. , Hisdal J. , Walløe L.
Published: December 2017

We have investigated the effect of severe local cooling on the vasomotor activity of the arteriovenous anastomoses (AVAs) and other finger vessels. The right third finger was subjected to local cooling (3°C) for 30–45 min in 21 healthy, thermoneutral subjects. Blood velocity in the third finger arteries of both hands was simultaneously recorded using ultrasound Doppler, and skin temperature and laser-Doppler flux from the pulp of the cooled finger were also recorded. The results demonstrate that the initial cold-induced vasoconstriction during severe local cooling involves constriction of the AVAs as well as the two main arteries supplying this finger. During cold-induced vasodilatation (CIVD), the maximum velocity values were not significantly different from those before cooling. Furthermore, the velocity fluctuations in the cooled finger were in most subjects found to be synchronous with the velocity fluctuations in the control finger. This indicates that the large blood flow to the finger and the high skin temperature during CIVD are caused by relaxation of the smooth muscle cells of the AVAs.