bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental changes in respiratory, febrile, and cardiovascular responses to PGE2 in newborn lambs
Authors: Tai T. C. , Adamson S. L.
Published: December 2017

PGE2 has centrally mediated respiratory, febrile, and cardiovascular effects that markedly differ between fetal and adult life. We hypothesized that the transition from fetal to adult responses to PGE2 occurs in the newborn period. Thus effects of an intracarotid infusion of PGE2 (3 μg/min for 60 min) were determined in unanesthetized newborn lambs at 5, 10, and 15 days after birth. At 5 days, PGE2 reduced central CO2 sensitivity, reduced lung ventilation due to a decrease in breathing frequency, and induced hypercapnia. By 15 days, these effects of PGE2 had waned significantly. In contrast, phasic (expiratory) thyroarytenoid muscle electromyogram activity, number of short apneas, and incidence of Biot periodic breathing were similarly increased at all three ages. PGE2 induced a sustained fever at 10 and 15 days. Heart rate and mean arterial blood pressure were unchanged in contrast to marked increases observed by others in adults. Results showed that the transition from fetal to adult respiratory and febrile responses to PGE2 occurs in early postnatal life, whereas adult cardiovascular responses develop later in life in sheep.
Endogenous tachykinins cause bradycardia by stimulating cholinergic neurons in the isolated guinea pig heart
Authors: Chang Yingzi , Hoover Donald B. , Hancock John C.
Published: December 2017

The purpose of this study was to determine if endogenous tachykinins can cause bradycardia in the isolated perfused guinea pig heart through stimulation of cholinergic neurons. Capsaicin was used to stimulate release of tachykinins and calcitonin gene-related peptide (CGRP) from cardiac afferents. A bolus injection of 100 nmol capsaicin increased heart rate by 26 ± 7% from a baseline of 257 ± 14 beats/min ( n = 6, P < 0.01). This positive chronotropic response was converted to a minor bradycardic effect in hearts with 1 μM CGRP-(8—37) present to block CGRP receptors. The negative chronotropic response to capsaicin was markedly potentiated in another group of hearts with the further addition of 0.5 μM neostigmine to inhibit cholinesterases. In this group, capsaicin decreased heart rate by 30 ± 10% from a baseline of 214 ± 6 beats/min ( n = 8, P < 0.05). This large bradycardic response to capsaicin was inhibited by 1) infusion of neurokinin A to desensitize tachykinin receptors or 2) treatment with 1 μM atropine to block muscarinic receptors. The latter observations implicate tachykinins and acetylcholine, respectively, as mediators of the bradycardia. These findings support the hypothesis that endogenous tachykinins could mediate axon reflexes to stimulate cholinergic neurons of the intrinsic cardiac ganglia.
Voltage-dependent calcium channels in ventricular cells of rainbow trout: effect of temperature changes in vitro
Authors: Kim Catherine S. , Coyne Mary D. , Gwathmey Judith K.
Published: December 2017

Voltage-dependent calcium channels (VDCC) in ventricular myocytes from rainbow trout ( Oncorhynchus mykiss) were investigated in vitro using the perforated patch-clamp technique, which maintains the integrity of the intracellular milieu. First, we characterized the current using barium as the charge carrier and established the doses of various pharmacological agents to use these agents in additional studies. Second, we examined the current at several physiological temperatures to determine temperature dependency. The calcium currents at 10°C (acclimation temperature) were identified as l-type calcium currents based on their kinetic behavior and response to various calcium channel agonists and antagonists. Myocytes were chilled (4°C) and warmed (18 and 22°C), and the response of VDCC to varying temperatures was observed. There was no significant dependency of the current amplitude and kinetics on temperature. Amplitude decreased 25–36% at 4°C (Q10∼1.89) and increased 18% at 18°C (Q10∼1.23) in control, Bay K8644 (Bay K)-, and forskolin-enhanced currents. The inactivation rates (τi) did not demonstrate a temperature sensitivity for the VDCC (Q101.23–1.92); Bay K treatment, however, increased temperature sensitivity of τibetween 10 and 18°C (Q103.98). The low Q10values for VDCC are consistent with a minimal temperature sensitivity of trout myocytes between 4 and 22°C. This low-temperature dependency may provide an important role for sarcolemmal calcium channels in adaptation to varying environmental temperatures in trout.
Hormonal regulation of expression of ileal bile acid binding protein in suckling rats
Authors: Hwang Sandy T. , Henning Susan J.
Published: December 2017

Ileal bile acid binding protein (IBABP) is a cytosolic protein believed to be involved in the absorption of conjugated bile acids. In rodents this protein and its mRNA have been shown to increase markedly during the third postnatal week. Because this period of ontogeny is characterized by increasing circulating concentrations of glucocorticoids and thyroxine, the goal of our study was to investigate the role of these hormones in IBABP expression in the developing rat. Administration of various doses of dexamethasone (Dex) during the second postnatal week caused a robust induction of IBABP mRNA and protein. Plateau levels of IBABP mRNA occurred at a Dex dose of 0.1 μg/g body wt, which is within the physiological range. IBABP mRNA was not appreciably induced until 24 h after treatment, suggesting that glucocorticoids influence IBABP either through a delayed primary or a secondary response mechanism. The regional pattern of IBABP mRNA elicited by Dex mimicked that seen during normal development, with appearance in distal ileum preceding proximal ileum. Thyroxine injections did not result in a significant increase of IBABP mRNA, and synergism between Dex and thyroxine was not observed. Taken together, our data suggest that maturation of IBABP expression is influenced by glucocorticoids but not by thyroxine.
GnRH stimulates LH release directly via inositol phosphate and indirectly via cAMP in African catfish
Authors: Rebers Frank E. M. , Bosma Peter T. , van Dijk Wytske , Goos Henk J. T. , Schulz Rüdiger W.
Published: December 2017

In African catfish, two gonadotropin-releasing hormone (GnRH) peptides have been identified: chicken GnRH (cGnRH)-II and catfish GnRH (cfGnRH). The GnRH receptors on pituitary cells producing gonadotropic hormone signal through inositol phosphate (IP) elevation followed by increases in intracellular calcium concentration ([Ca2+]i). In primary pituitary cell cultures of male African catfish, both cGnRH-II and cfGnRH dose dependently elevated IP accumulation, [Ca2+]i, and the release of the luteinizing hormone (LH)-like gonadotropin. In all cases, cGnRH-II was more potent than cfGnRH. The GnRH-stimulated LH release was not associated with elevated cAMP levels, and forskolin-induced cAMP elevation had no effect on LH release. With the use of pituitary tissue fragments, however, cAMP was elevated by GnRH, and forskolin was able to stimulate LH secretion. Incubating these fragments with antibodies against cfGnRH abolished the forskolin-induced LH release but did not compromise the forskolin-induced cAMP elevation. This suggests that cfGnRH-containing nerve terminals are present in pituitary tissue fragments and release cfGnRH via cAMP signaling on GnRH stimulation, whereas the GnRH receptors on gonadotrophs use IP/[Ca2+]ito stimulate the release of LH.
A projection from the ventral tegmental area to the periaqueductal gray involved in cardiovascular regulation
Authors: Kirouac Gilbert J. , Pittman Quentin J.
Published: December 2017

Experiments were done in α-chloralose-anesthetized rats to determine a pathway mediating the cardiovascular depressor responses elicited from stimulation of the ventral tegmental area (VTA). The magnitude of the depressor responses elicited by glutamate stimulation (0.1 M/30 nl) of the VTA was examined after neuronal block produced by microinjections of lidocaine into ascending fiber bundles leaving the VTA to innervate the forebrain and thalamus. Bilateral microinjections of 1 μl of 4% lidocaine in the medial forebrain bundle ( n = 6) and in the periventricular fibers of the midbrain ( n = 5) did not attenuate the depressor response from stimulation of the VTA. Experiments were done using the anterograde tracer biotinylated dextran amine to identify descending projections from the VTA to cardiovascular centers in the brain stem. Examination of the nucleus of the solitary tract, ventrolateral medulla, and A5 catecholaminergic cell group revealed few or no fibers or terminals. Occasional fibers and some terminals were observed in the nucleus of raphe magnus, parabrachial nucleus, and locus ceruleus. A very dense bilateral projection was found to the ventrolateral periaqueductal gray (PAGvl) and dorsal raphe nucleus adjacent to the PAGvl. Bilateral injections of 4% lidocaine ( n = 4) or 10 mM cobalt chloride ( n = 5) into the PAGvl region attenuated the depressor responses elicited by stimulation of the VTA by ∼50%. These experiments indicate that the depressor responses elicited from activation of the VTA are mediated in part by a pathway to a cardiovascular depressor area located in the PAGvl.
Evidence for an intrarenal renin-angiotensin system in the rainbow trout,Oncorhynchus mykiss
Authors: Brown J. Anne , Paley Richard K. , Amer Shehla , Aves Stephen J.
Published: December 2017

Physiological and molecular approaches were used to investigate the existence of an intrarenal renin-angiotensin system (RAS) in rainbow trout. Inhibition of angiotensin-converting enzyme by captopril (5 × 10−4M) rapidly decreased vascular resistance of the trunk of the trout, perfused at 19 mmHg, resulting in an increased perfusate flow rate and a decreased intrarenal dorsal aortic pressure. A profound diuresis occurred in the in situ perfused kidney and reflected both increased glomerular filtration rates and decreased water reabsorption (osmolyte reabsorption was unchanged). Renal and vascular parameters recovered once captopril treatment was stopped. Diuretic and vascular effects of captopril on the in situ trout kidney concur with an inhibition of known vasoconstrictor and antidiuretic actions of angiotensin II. However, at a higher perfusion pressure (28 mmHg), captopril had no effect on intrarenal aortic pressure or perfusate and urine flow rates, suggesting that the trout intrarenal RAS is activated by low perfusion pressures/flows. Existence of the renal RAS in trout was further supported by evidence for angiotensinogen gene expression in kidney as well as liver.
Multiple comparisons: philosophies and illustrations
Authors: Curran-Everett Douglas
Published: December 2017

Statistical procedures underpin the process of scientific discovery. As researchers, one way we use these procedures is to test the validity of a null hypothesis. Often, we test the validity of more than one null hypothesis. If we fail to use an appropriate procedure to account for this multiplicity, then we are more likely to reach a wrong scientific conclusion—we are more likely to make a mistake. In physiology, experiments that involve multiple comparisons are common: of the original articles published in 1997 by the American Physiological Society, ∼40% cite a multiple comparison procedure. In this review, I demonstrate the statistical issue embedded in multiple comparisons, and I summarize the philosophies of handling this issue. I also illustrate the three procedures—Newman-Keuls, Bonferroni, least significant difference—cited most often in my literature review; each of these procedures is of limited practical value. Last, I demonstrate the false discovery rate procedure, a promising development in multiple comparisons. The false discovery rate procedure may be the best practical solution to the problems of multiple comparisons that exist within physiology and other scientific disciplines.
Electrical stimulation of afferent vagus nerve induces IL-1β expression in the brain and activates HPA axis
Authors: Hosoi Toru , Okuma Yasunobu , Nomura Yasuyuki
Published: December 2017

Possible roles of the afferent vagus nerve in regulation of interleukin (IL)-1β expression in the brain and hypothalamic-pituitary-adrenal (HPA) axis were examined in anesthetized rats. Levels of IL-1β mRNA and protein in the brain were measured by comparative RT-PCR and ELISA. Direct electrical stimulation of the central end of the vagus nerve was performed continuously for 2 h. The afferent stimulation of the vagus nerve induced increases in the expression of mRNA and protein levels of IL-1β in the hypothalamus and the hippocampus. Furthermore, expression of corticotropin-releasing factor mRNA was increased in the hypothalamus 2 h after vagal stimulation. Plasma levels of ACTH and corticosterone were also increased by this stimulation. The present results indicate that activation of the afferent vagus nerves itself can induce production of IL-1β in the brain and activate the HPA axis. Therefore, the afferent vagus nerve may play an important role in transmitting peripheral signals to the brain in the infection and inflammation.
Effect of acute hypoxia on vasopressin release and intravascular fluid during dynamic exercise in humans
Authors: Takamata Akira , Nose Hiroshi , Kinoshita Takashi , Hirose Munetaka , Itoh Toshiyuki , Morimoto Taketoshi
Published: December 2017

To test the hypothesis that acute hypoxia does not modify the relationship between plasma vasopressin concentration ([AVP]p) and plasma osmolality (Posmol) during exercise and that the increase in [AVP]p during exercise is due mainly to the exercise intensity-dependent increase in Posmol, we examined [AVP]p during a graded exercise in a hypoxic condition (13% O2, N2 balance) in seven healthy male subjects. A graded exercise in a normoxic condition on a separate day served as the control. Hypoxia reduced peak aerobic power (V˙o 2 peak) by 32.4 ± 2.7%. Blood samples obtained during rest and at around 25, 45, 65, 80, and 100% ofV˙o 2 peak of each of the respective conditions were used for analyses of intravascular water and electrolyte balance. The pattern of the changes in fluid and electrolyte balance in response to percentV˙o 2 peak was similar between the two conditions. Plasma volume decreased linearly as percentV˙o 2 peak increased while Posmol increased in a curvilinear fashion with a steep increase occurring at above ∼66%V˙o 2 peak. Above this relative exercise intensity, plasma sodium, potassium, and lactate concentrations also increased, whereas plasma bicarbonate concentration decreased. Thus transvascular fluid movement at above ∼66%V˙o 2 peak was due to the net efflux of hypotonic fluid out of the vascular space in both conditions. The relationship between [AVP]p and Posmol during exercise in response to relative exercise intensity was similar between the two conditions. The results indicate that acute mild hypoxia itself has no direct effect on vasopressin release, and it does not modify the relationship between [AVP]p and Posmol during exercise. The results also support the hypothesis that exercise-induced vasopressin release is primarily stimulated by increased Posmol produced by hypotonic fluid movement out of the vascular space in a relative exercise intensity-dependent manner.
Interaction between CCK and a preload on reduction of food intake is mediated by CCK-A receptors in humans
Authors: Gutzwiller Jean-Pierre , Drewe Juergen , Ketterer Silvia , Hildebrand Pius , Krautheim Alexandra , Beglinger Christoph
Published: December 2017

Cholecystokinin (CCK) interacts with neural signals to induce satiety in several species, but the mechanisms are unclear. We therefore tested the hypothesis that alimentary CCK (CCK-A) receptors mediate the interaction of CCK with an appetizer on food intake in humans. CCK octapeptide (CCK-8, 0.75 μg infused over 10 min) or saline (placebo) with concomitant infusions of saline (placebo) or loxiglumide, a specific CCK-A antagonist, was infused into 16 healthy men with use of a double-blind, four-period design. All subjects received a standard 400-ml appetizer (amounting to 154 kcal) but were free to eat and drink thereafter as much as they wished. The effect of these infusions on feelings of hunger and satiety and on food intake was quantified. CCK-8 induced a reduction in calorie intake ( P < 0.05) compared with saline. Furthermore, a decrease in hunger feelings ( P < 0.05, saline-CCK-8 vs. all other treatments) and an increase in fullness were observed. These effects were antagonized for hunger and fullness by loxiglumide. We conclude that CCK-8 interacts with an appetizer to modulate satiety in humans. These effects are mediated by CCK-A receptors.
Postprandial metabolism and aversive response in rats fed a threonine-devoid diet
Authors: Even P. C. , Rolland V. , Feurté S. , Fromentin G. , Roseau S. , Nicolaïdis S. , Tomé D.
Published: December 2017

Lack of an indispensable amino acid in the diet induces a rapid reduction in food intake. In this study, we assessed whether the anorectic signal after ingestion of a meal lacking threonine originated from either direct perception of the decrease in plasma threonine or from an indirect effect related to increased postprandial amino acid catabolism and energy expenditure. We observed that 3 g of such a meal was sufficient to induce an aversive response to the diet within 2 h. Postprandial changes to plasma ammonia and urea, urinary urea, and energy metabolism did not differ from those measured after a control meal. In contrast, plasma threonine levels fell within 1 h after the meal. It is concluded that an increase in postprandial energy expenditure is not involved in the anorectic response to eating a threonine-devoid diet. The drop in plasma threonine levels may be a potential signal, but the fact that the decrease in food intake occurred 1 h after the decrease in plasma threonine questions a direct causal relationship.
Tissue hypoxia inhibits prostaglandin and nitric oxide production and prevents ductus arteriosus reopening
Authors: Kajino Hiroki , Chen Yao-Qi , Chemtob Sylvain , Waleh Nahid , Koch Cameron J. , Clyman Ronald I.
Published: December 2017

Regulation of ductus arteriosus (DA) tension depends on a balance between oxygen-induced constriction and PG and nitric oxide (NO)-mediated relaxation. After birth, increasing PaO2 produces DA constriction. However, as the full-term ductus constricts, it develops severe tissue hypoxia in its inner vessel wall (oxygen concentration <0.2%). We used isolated rings of fetal lamb DA to determine why the constricted ductus does not relax and reopen as it becomes hypoxic. We used a modification of the 2-(2-nitro-1 H-imidazol-1-yl)- N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF5) technique (Clyman RI, Chan CY, Mauray F, Chen YQ, Cox W, Seidner SR, Lord EM, Weiss H, Wale N, Evan SM, and Koch CJ. Pediatr Res 45: 19–29, 1999) to determine mean tissue oxygen concentration. A decrease in the ductus' mean tissue oxygen concentration from 1.4 to 0.1% lowers the isometric tone of the ductus by 15 ± 10% of its maximal active tension (the maximal tension that can be produced by the ductus). Although decreases in oxygen concentration diminish ductus tension, most of the vasoconstrictor tone in the ductus is independent of ambient oxygen concentration. This oxygen-independent tone is equivalent to 64 ± 10% of the maximal active tension. At mean tissue oxygen concentrations >0.2%, endogenous PGs and NO inhibit more than 40% of the active tension developed by the ductus. However, when tissue oxygen concentrations drop below 0.2%, the constitutive relaxation of the ductus by endogenous PGs and NO is lost. In the absence of PG and NO production, tension increases to a level normally observed only after treatment of the ductus with indomethacin and nitro-l-arginine methyl ester (inhibitors of PG and NO production). Therefore, under conditions of severe hypoxia (tissue oxygen concentration <0.2% oxygen), the loss of PG- and NO-mediated relaxation more than compensates for the loss of oxygen-induced tension. We hypothesize that this increased ductus tone enables the vessel to remain closed as it undergoes tissue remodeling.
Reduced fetal, placental, and amniotic fluid PTHrP in the growth-restricted spontaneously hypertensive rat
Authors: Wlodek Mary E. , Westcott Kerryn T. , Ho Patricia W. M. , Serruto Anne , Di Nicolantonio Robert , Farrugia William , Moseley Jane M.
Published: December 2017

Evidence implicates pivotal roles for parathyroid hormone-related protein (PTHrP) in stimulating cell growth and differentiation, placental calcium transport, and placental vasodilatation. As spontaneously hypertensive rat (SHR) fetuses are growth restricted compared with those of its normotensive control, the Wistar Kyoto (WKY) rat, we examined intrauterine PTHrP and total and ionic calcium concentrations in these rats. Fetal plasma PTHrP concentrations, but not total calcium concentrations, were lower in the SHR compared with WKY ( P< 0.05). SHR placental concentrations of PTHrP were lower than in WKY ( P < 0.03) and failed to show the increase observed in WKY near term ( P < 0.05). PTHrP concentrations in amniotic fluid from SHR were not raised near term and were lower compared with WKY ( P < 0.0005). The increased ionic calcium concentrations in amniotic fluid in the WKY near term ( P < 0.05) were not detected in the SHR. Thus SHR fetal plasma, placental, and amniotic fluid PTHrP concentrations were reduced and associated with fetal growth restriction. We suggest that PTHrP may play a role in the etiology of both growth restriction during pregnancy and hypertension later in life.
Nifedipine-induced inhibition of parasympathetic-mediated vasodilation in the orofacial areas of the cat
Authors: Izumi Hiroshi , Nakamura Ikuko
Published: December 2017

In anesthetized cats, we 1) compared the effects of antihypertensive agents (nifedipine, clonidine, phentolamine, propranolol, and nitroprusside) on the parasympathetic vasodilations elicited by lingual nerve (LN) stimulation in the lower lip and tongue and 2) investigated the mechanisms underlying the inhibitory effect of nifedipine on parasympathetic lower lip vasodilation. At the doses used, each antihypertensive agent reduced systemic arterial blood pressure by ∼20 mmHg; however, the parasympathetic vasodilation elicited by LN stimulation was significantly reduced only by nifedipine. This inhibitory effect of nifedipine was not seen when LN was stimulated during ongoing repetitive stimulation of the superior cervical sympathetic trunk at 1-Hz frequency. This suggests that the ability of lip and tongue blood vessels to relax to parasympathetic stimulation is not directly impaired by this calcium channel blocker and that the inhibitory effects of nifedipine seen here probably resulted from an action on postsynaptic sites in vascular smooth muscle that caused a reduction in preexisting sympathetic vasoconstrictor tone (by inhibiting calcium influx into the vascular smooth muscle cell).
Regulation of urinary bladder smooth muscle contractions by ryanodine receptors and BK and SK channels
Authors: Herrera Gerald M. , Heppner Thomas J. , Nelson Mark T.
Published: December 2017

This study examines the roles of voltage-dependent Ca2+channels (VDCC), ryanodine receptors (RyRs), large-conductance Ca2+-activated K+(BK) channels, and small-conductance Ca2+-activated K+(SK) channels in the regulation of phasic contractions of guinea pig urinary bladder smooth muscle (UBSM). Nisoldipine (100 nM), a dihydropyridine inhibitor of VDCC, abolished spontaneous UBSM contractions. Ryanodine (10 μM) increased contraction frequency and thereby integrated force and, in the presence of the SK blocker apamin, had a greater effect on integrated force than ryanodine alone. Blocking BK (iberiotoxin, 100 nM) or SK (apamin, 100 nM) channels increased contraction amplitude and duration but decreased frequency. The contractile response to iberiotoxin was more pronounced than to apamin. The increases in contraction amplitude and duration to apamin were substantially augmented with ryanodine pretreatment. These results indicate that BK and SK channels have prominent roles as negative feedback elements to limit UBSM contraction amplitude and duration. RyRs also appear to play a significant role as a negative feedback regulator of contraction frequency and duration, and this role is influenced by the activity of SK channels.
Osmolyte channel regulation by ionic strength in skate RBC
Authors: Wittels Kathleen A. , Hubert Elise M. , Musch Mark W. , Goldstein Leon
Published: December 2017

The aim of this study was to determine whether the opening of the osmolyte channel in skate red blood cells (RBC) is regulated by intracellular electrolyte concentration and conductivity. Consistent with previous studies, experiments with hyperosmotic preincubation before cell swelling or swelling with an isosmotic electrolyte (e.g., ammonium chloride) showed that an increase in ionic strength inhibits the opening of the taurine channel. However, a decrease in intracellular ionic strength did not always stimulate taurine efflux to the same degree. Whereas hyposmotic swelling caused a large increase in taurine efflux, swelling induced by treatment with isosmotic nonelectrolytes produced much smaller stimulation. Results with assays for band 3 phosphorylating enzymes were consistent with those from the taurine efflux studies; stimulation of enzyme activity was lower in cells that were swollen with isosmotic nonelectrolyte media than in cells swollen in hyposmotic media. These results indicate that a decrease in ionic strength is not the only signal for the opening of the taurine channel in skate RBC. Ionic strength does affect channel activity, but there must also be some other regulator.
Critical oxygen tension in rat brain: a combined31P-NMR and EPR oximetry study
Authors: Rolett Ellis L. , Azzawi Ali , Liu Ke Jian , Yongbi Martin N. , Swartz Harold M. , Dunn Jeff F.
Published: December 2017

The relationship between cerebral interstitial oxygen tension (PtO2) and cellular energetics was investigated in mechanically ventilated, anesthetized rats during progressive acute hypoxia to determine whether there is a “critical” brain PtO2for maintaining steady-state aerobic metabolism. Cerebral PtO2, measured by electron paramagnetic resonance oximetry, decreased proportionately to inspired oxygen fraction.31P-nuclear magnetic resonance measurements revealed no changes in Pi, phosphocreatine (PCr)/Piratio, or intracellular pH when arterial blood oxygen tension (PaO2) was reduced from 145.1 ± 11.7 to 56.5 ± 4.4 mmHg (means ± SE). Intracellular acidosis, a sharp rise in Pi, and a decline in the PCr/Piratio developed when PaO2was reduced further to 40.7 ± 2.3 mmHg. The corresponding PtO2values were 15.1 ± 1.8, 8.8 ± 0.4, and 6.8 ± 0.3 mmHg. We conclude that over a range of decreasing oxygen tensions, cerebral oxidative metabolism is not sensitive to oxygen concentration. Oxygen becomes a regulatory substrate, however, when PtO2is decreased to a critical level.
Intracellular pH regulation in neurons from chemosensitive and nonchemosensitive regions of Helix aspersa
Authors: Goldstein Jonathan I. , Mok James M. , Simon Christopher M. , Leiter J. C.
Published: December 2017

We used 2′,7′-bis(carboxyethyl)-5(6)-carboxyflourescein (BCECF), a pH-sensitive fluorescent dye, to study intracellular pH (pHi) regulation in neurons in CO2chemoreceptor and nonchemoreceptor regions in the pulmonate, terrestrial snail, Helix aspersa. We studied pHiduring hypercapnic acidosis, after ammonia prepulse, and during isohydric hypercapnia. In all treatment conditions, pHifell to similar levels in chemoreceptor and nonchemoreceptor regions. However, pHi recovery was consistently slower in chemoreceptor regions compared with nonchemoreceptor regions, and pHi recovery was slower in all regions when extracellular pH (pHe) was also reduced. We also studied the effect of amiloride and DIDS on pHi regulation during isohydric hypercapnia. An amiloride-sensitive mechanism was the dominant pHi regulatory process during acidosis. We conclude that pHe modulates and slows pHiregulation in chemoreceptor regions to a greater extent than in nonchemoreceptor regions by inhibiting an amiloride-sensitive Na+/H+ exchanger. Although the phylogenetic distance between vertebrates and invertebrates is large, similar results have been reported in CO2-sensitive regions within the rat brain stem.
PACAP contributes to insulin secretion after gastric glucose gavage in mice
Authors: Filipsson Karin , Holst Jens Juul , Ahrén Bo
Published: December 2017

Pituitary adenylate cyclase-activating polypeptide (PACAP) is localized to pancreatic ganglia governing the parasympathetic nerves, which contribute to prandial insulin secretion. We hypothesized that this contribution involves PACAP and show here that the PACAP receptor antagonist PACAP-(6—27) (1.5 nmol/kg iv) reduces the 15-min insulin response to gastric glucose (150 mg/mouse) by 18% in anesthetized mice ( P = 0.041). The reduced insulinemia was not due to inhibited release of the incretin factor glucagon-like peptide 1 (GLP-1) because PACAP-(6—27) enhanced the GLP-1 response to gastric glucose. Furthermore, the GLP-1 antagonist exendin-3-(9—39) (30 nmol/kg) exerted additive inhibitory effect on the insulin response when combined with PACAP-(6—27). The PACAP antagonism was specific because intravenous PACAP-(6—27) inhibited the insulin response to intravenous PACAP-27 plus glucose without affecting the insulin response to intravenous glucose alone (1 g/kg) or glucose together with other insulin secretagogues of potential incretin relevance of intestinal (GLP-1, gastric inhibitory polypeptide, cholecystokinin) and neural (vasoactive intestinal peptide, gastrin-releasing peptide, cholinergic agonism) origin. We conclude that PACAP contributes to the insulin response to gastric glucose in mice and suggest that PACAP is involved in the regulation of prandial insulin secretion.
Role of cytochromeP-450 in endogenous antipyresis
Authors: Kozak Wieslaw , Kluger Matthew J. , Kozak Anna , Wachulec Maciej , Dokladny Karol
Published: December 2017

In previous reports, we (15, 18) and others (29) demonstrated data showing that various inhibitors of cytochrome P-450/epoxygenase augment fever in rats and mice, indicating that the enzyme may be involved in endogenous antipyresis. The aim of this study was to further test the hypothesis that the P-450-dependent epoxygenase pathway of arachidonic acid is part of the homeostatic system to control the height of fever. Sprague-Dawley rats were implanted with biotelemeters to monitor body temperature. Fever was induced by intraperitoneal injection of lipopolysaccharide (LPS; 80 μg/kg). We demonstrate that intraperitoneal administration of P-450 inducers (bezafibrate and dehydroepiandrosterone, 10 and 100 mg/kg) before LPS reduced fever in rats in a dose-dependent manner. In complementary experiments, rats were implanted with brain cannulas in addition to the biotelemeters. Various isomers of epoxyeicosanoids were administered into the lateral ventricle at doses of 0.01 to 10 μg/rat to test their influence on LPS-induced fever in rats. Four of five isomers were antipyretic in a dose-dependent manner. The most potent antipyretic isomers were 11,12-epoxyeicosatrienoic acid (EET) followed by 14,15-EET, 8,9-EET, and 12(R) hydroxyeicosatetraenoic acid. These data support the hypothesis that the cytochrome P-450/epoxygenase pathway of arachidonate metabolism is part of the endogenous antipyretic system.
Stress causes decrease in vascular relaxation linked with altered phosphorylation of heat shock proteins
Authors: Fuchs Leslie C. , Giulumian Ararat D. , Knoepp Louis , Pipkin Walter , Dickinson Mary , Hayles Chad , Brophy Colleen
Published: December 2017

Cyclic nucleotide-dependent vascular relaxation is associated with increases in the phosphorylation of a small heat shock protein (HSP), HSP20. An increase in phosphorylation of another small HSP, HSP27, is associated with impaired cyclic nucleotide-dependent vascular relaxation. Expression of HSPs is altered by exposure to several types of cellular stress in vitro. To determine if behavioral stress in vivo alters vascular expression and phosphorylation of the small HSPs and cyclic nucleotide-dependent vascular relaxation, borderline hypertensive rats were stressed by restraint and exposure to air-jet stress 2 h/day for 10 days or remained in their home cage. Stress impaired relaxation of aorta to forskolin, which activates adenylyl cyclase, and sodium nitroprusside, which activates guanylyl cyclase. This was associated with an increase in the aortic expression and phosphorylation of HSP27, which was localized to the vascular smooth muscle, but a decrease in the amount of phosphorylated (P)-HSP20. To determine if P-HSP27 inhibits phosphorylation of HSP20, P-HSP27 was added to a reaction mixture containing recombinant HSP20 and the catalytic subunit of cAMP-dependent protein kinase. P-HSP27 inhibited phosphorylation of HSP20 in a concentration-dependent manner. These data demonstrate that P-HSP27 can inhibit phosphorylation of HSP20. The increase in P-HSP27 and decrease in P-HSP20 were associated with reduced cyclic nucleotide-dependent vascular smooth muscle relaxation in response to behavioral stress in vivo, an effect similar to that observed previously in response to cellular stress in vitro.
Cardiovascular actions of python bradykinin and substance P in the anesthetized python,Python regius
Authors: Wang Tobias , Axelsson Michael , Jensen Jorgen , Conlon J. Michael
Published: December 2017

The cardiovascular actions of python bradykinin (BK) and substance P (SP) have been investigated in the anesthetized ball python, Python regius. Bolus intra-arterial injections of python BK (0.03–3 nmol/kg) produced concentration-dependent increases in arterial blood pressure, heart rate (HR), and cardiac output concomitant with small decreases in systemic resistance and stroke volume. Intra-arterial injection of 3 nmol/kg python BK produced a tenfold increase in circulating concentration of norepinephrine, but epinephrine levels did not change. BK-induced tachycardia was attenuated (>90%) by the β-adrenergic receptor antagonist sotalol, and the hypertensive response was attenuated (>70%) by the α-adrenergic receptor antagonist prazosin, indicating that effects of python BK are mediated at least in part by activation of the extensive network of adrenergic neurons present in vascular tissues. Bolus intra-arterial injections of python SP in the range 0.01–30 pmol/kg produced concentration-dependent decreases in arterial blood pressure and systemic peripheral resistance concomitant with increases in cardiac output and stroke volume but with only minor effects on HR. The data suggest that kinins play a physiologically important role in cardiovascular regulation in the python.
Cardiorespiratory responses of white sturgeon to environmental hypercapnia
Authors: Crocker Carlos E. , Farrell Anthony P. , Gamperl A. Kurt , Cech Joseph J.
Published: December 2017

Cardioventilatory variables and blood-gas, acid-base status were measured in cannulated white sturgeon ( Acipenser transmontanus) maintained at 19°C during normocapnic and hypercapnic (PwCO2∼20 Torr) water conditions and after the injection of adrenergic analogs. Hypercapnia produced significant increases in arterial Pco2, ventilatory frequency, and plasma concentration of cortisol and epinephrine, and it produced significant decreases in arterial pH and plasma concentration of glucose but no change in arterial Po2, hematocrit, and concentration of lactate or norepinephrine. Hypercapnia significantly increased cardiac output (Q) by 22%, mean arterial pressure (MAP) by 8%, and heart rate (HR) by 8%. However, gut blood flow (GBF) remained constant. In normocapnic fish, phenylephrine significantly constricted the splanchnic circulation, whereas isoproterenol significantly increased Q and produced a systemic vasodilation. During hypercapnia, propranolol significantly decreased Q, GBF, MAP, and HR, whereas phentolamine significantly decreased MAP and increased GBF. These changes suggest that cardiovascular function in the white sturgeon is sensitive to both α- and β-adrenergic modulation. We found microspheres to be unreliable in predicting GBF on the basis of our comparisons with simultaneous direct measurements of GBF. Overall, our results demonstrate that environmental hypercapnia (e.g., as is experienced in high-intensity culture situations) elicits stress responses in white sturgeon that significantly elevate steady-state cardiovascular and ventilatory activity levels.
Relative magnitude of tonic and phasic synaptic excitation of medullary inspiratory neurons in dogs
Authors: Krolo M. , Stuth E. A. , Tonkovic-Capin M. , Hopp F. A. , McCrimmon D. R. , Zuperku E. J.
Published: December 2017

The relative contribution of phasic and tonic excitatory synaptic drives to the augmenting discharge patterns of inspiratory (I) neurons within the ventral respiratory group (VRG) was studied in anesthetized, ventilated, paralyzed, and vagotomized dogs. Multibarrel micropipettes were used to record simultaneously single-unit neuronal activity and pressure microejected antagonists of GABAergic, glycinergic, N-methyl-d-aspartate (NMDA) and non-NMDA glutamatergic, and cholinergic receptors. The discharge patterns were quantified via cycle-trigger histograms. The findings suggest that two-thirds of the excitatory drive to caudal VRG I neurons is tonic and mediated by NMDA receptors and the other third is ramp-like phasic and mediated by non-NMDA receptors. Cholinergic receptors do not appear to be involved. The silent expiratory phase is produced by phasic inhibition of the tonic activity, and ≈80% of this inhibition is mediated by γ-aminobutyric acid receptors (GABAA) and ≈20% by glycine receptors. Phasic I inhibition by the I decrementing neurons does not appear to contribute to the predominantly step-ramp patterns of these I neurons. However, this decrementing inhibition may be very prominent in controlling the rate of augmentation in late-onset I neurons and those with ramp patterns lacking the step component.
Molecular and kinetic characterization and cell type location of inducible nitric oxide synthase in fish
Authors: Barroso Juan B. , Carreras Alfonso , Esteban Francisco J. , Peinado María A. , Martínez-Lara Esther , Valderrama Raquel , Jiménez Ana , Rodrigo José , Lupiáñez José A.
Published: December 2017

We have found conclusive evidence for inducible nitric oxide synthase (iNOS) activity in rainbow trout ( Oncorhynchus mykiss) tissue by means of biochemical, immunohistochemical, and immunoblotting analyses. This Ca2+-independent enzyme uses l-arginine to produce nitric oxide and l-citrulline. It was significantly inhibited by the l-arginine analogs Nω-monomethyl-l-arginine and NG-nitro-l-arginine methyl ester. Kinetic analyses showed typical Michaelian behavior with no evidence of cooperative effects. The specific activities of the liver and head kidney enzymes were 27 and 106 pmoles · min−1· mg protein−1, respectively, with similar values for Km(11 μM), all of which correspond well with the values for other previously characterized iNOS. Western blot analyses revealed a single band of MR= 130 kDa tested with an iNOS antiserum. At the ultrastructural level, cells with NADPH-diaphorase activity and iNOS immunoreactivity were identified as being heterophilic granulocytes in head kidney tissue and neutrophils and macrophages in hepatic tissue. The presence of an iNOS isoform in these fish tissues implies that these cells are capable of generating nitric oxide, thus pointing to the potential role of this enzyme in fish defense mechanisms.
The biomechanics and evolutionary significance of thermal acclimation in the common carpCyprinus carpio
Authors: Wakeling James M. , Cole Nicholas J. , Kemp Kirsty M. , Johnston Ian A.
Published: December 2017

The effects of thermal acclimation were investigated in the common carp Cyprinus carpio L. Acclimation and acute temperature effects were tested during ontogeny from larval [9.5 mm total length ( L)] to juvenile (69.0 mm L) stages and between 8 and 21°C. The myosin heavy chain (MHC) composition, myofibrillar Mg2+-Ca2+-ATPase activity, and muscle strains showed significant thermal acclimation effects. MHCs were only expressed in an acclimation temperature-dependent fashion in fish longer than 37 mm. During fast starts, the temperature had a significant effect on the white muscle strain (33% increase and 50% decrease with increasing acclimation and acute temperature, respectively) and contraction duration (25% decrease with increasing acute temperature). Increases in hydrodynamic efficiency (0.19 to 0.38) and hydrodynamic power requirements (Q10= 3.2) occurred with increasing acute temperature (10 to 20 °C). Competing hypotheses about the evolutionary significance of the temperature acclimation response were tested. Acclimation extended the temperature range for fast-start behavior, but no improvements in performance at the whole animal level were found between 8 and 21°C.
Effect of intracerebroventricular α-MSH on food intake, adiposity, c-Fos induction, and neuropeptide expression
Authors: McMinn Julie E. , Wilkinson Charles W. , Havel Peter J. , Woods Stephen C. , Schwartz Michael W.
Published: December 2017

α-Melanocyte-stimulating hormone (α-MSH) is a hypothalamic neuropeptide proposed to play a key role in energy homeostasis. To investigate the behavioral, metabolic, and hypothalamic responses to chronic central α-MSH administration, α-MSH was infused continuously into the third cerebral ventricle of rats for 6 days. Chronic α-MSH infusion reduced cumulative food intake by 10.7% ( P < 0.05 vs. saline) and body weight by 4.3% ( P < 0.01 vs. saline), which in turn lowered plasma insulin levels by 29.3% ( P < 0.05 vs. saline). However, α-MSH did not cause adipose-specific wasting nor did it alter hypothalamic neuropeptide mRNA levels. Central α-MSH infusion acutely activated neurons in forebrain areas such as the hypothalamic paraventricular nucleus, as measured by a 254% increase in c-Fos-like immunoreactivity ( P < 0.01 vs. saline), as well as satiety pathways in the hindbrain. Our findings suggest that, although an increase of central melanocortin receptor signaling acutely reduces food intake and body weight, its anorectic potency wanes during chronic infusion and causes only a modest decrease of body weight.
Effect of severe normocapnic hypoxia on renal function in growth-restricted newborn piglets
Authors: Bauer Reinhard , Walter Bernd , Zwiener Ulrich
Published: December 2017

To examine the effects of intrauterine growth restriction and acute severe oxygen deprivation on renal blood flow (RBF), renovascular resistance (RVR), and renal excretory functions in newborns, studies were conducted on 1-day-old anesthetized piglets divided into groups of normal weight (NW, n = 14) and intrauterine growth-restricted (IUGR, n = 14) animals. Physiological parameters, RBF, RVR, and urinary flow, were similar in NW and IUGR piglets, but glomerular filtration rate (GFR) and filtration fraction were significantly less in IUGR animals ( P < 0.05). An induced 1-h severe hypoxia (arterial Po 2 = 19 ± 4 mmHg) resulted in, for both groups, a pronounced metabolic acidosis, strongly reduced RBF, and increased fractional sodium excretion (FSE; P < 0.05) with a less-pronounced increase of RVR and arterial catecolamines in IUGR piglets. Of significance was a smaller decrease in RBF for IUGR piglets ( P < 0.05). Early recovery showed a transient period of diuresis with increased osmotic clearance and elevated FSE in both groups ( P < 0.05). However, GFR and renal O2 delivery remained reduced in NW piglets ( P < 0.05). We conclude that, in newborn IUGR piglets, RBF is maintained, although GFR is compromised. Severe hypoxemia induces similar alterations of renal excretion in newborn piglets. However, the less-pronounced RBF reduction during hypoxemia indicates an improved adaptation of newborn IUGR piglets on periods of severely disturbed oxygenation. Furthermore, newborn piglets reestablish the ability for urine concentration and adequate sodium reabsorption early after reoxygenation so that a sustained acute renal failure was prevented.
Role of the renin-angiotensin system in regulation and autoregulation of renal blood flow
Authors: Sorensen Charlotte Mehlin , Leyssac Paul Peter , Skott Ole , Holstein-Rathlou Niels-Henrik
Published: December 2017

The role for ANG II in renal blood flow (RBF) autoregulation is unsettled. The present study was designed to test the effect of clamping plasma ANG II concentrations ([ANG II]) by simultaneous infusion of the angiotensin-converting enzyme inhibitor captopril and ANG II on RBF autoregulation in halothane-anesthetized Sprague-Dawley rats. Autoregulation was defined as the RBF response to acute changes in renal perfusion pressure (RPP). Regulation was defined as changes in RBF during long-lasting changes in RPP. The results showed that a prolonged reduction of RPP reset the lower limit of autoregulation from 85 ± 1 to 73 ± 2 mmHg ( P < 0.05) and regulated RBF to a lower level. Reduction of RPP to just above the lower limit of autoregulation (88 mmHg) induced regulation of RBF to a lower level within 10 min. Clamping [ANG II] per se reset the lower limit of autoregulation to 62 ± 5 mmHg. In this case, reduction in RPP to 50 mmHg did not induce a downregulation of RBF. We conclude that ANG II plays an important role in the resetting of the autoregulation limits. The ability to regulate RBF to a new level as a response to changes in RPP also depends on changes in [ANG II].
Regulation of food intake by neuropeptide Y in goldfish
Authors: Narnaware Yuwaraj K. , Peyon Pierre P. , Lin Xinwei , Peter Richard E.
Published: December 2017

In mammals, neuropeptide Y (NPY) is a potent orexigenic factor. In the present study, third brain ventricle (intracerebroventricular) injection of goldfish NPY (gNPY) caused a dose-dependent increase in food intake in goldfish, and intracerebroventricular administration of NPY Y1-receptor antagonist BIBP-3226 decreased food intake; the actions of gNPY were blocked by simultaneous injection of BIBP-3226. Goldfish maintained on a daily scheduled feeding regimen display an increase in NPY mRNA levels in the telencephalon-preoptic area and hypothalamus shortly before feeding; however, a decrease occured in optic tectum-thalamus. In both fed and unfed fish, brain NPY mRNA levels decreased after scheduled feeding. Restriction in daily food ration intake for 1 wk or food deprivation for 72 h resulted in increased brain NPY mRNA levels. Results from these studies demonstrate that NPY is a physiological brain signal involved in feeding behavior in goldfish, mediating its effects, at least in part, through Y1-like receptors in the brain.
Ontogeny of cholinergic and adrenergic cardiovascular regulation in the domestic chicken (Gallus gallus)
Authors: Crossley Dane , Altimiras Jordi
Published: December 2017

Adrenergic and cholinergic tone on the cardiovascular system of embryonic chickens was determined during days 12, 15, 19, 20, and 21 of development. Administration of the muscarinic antagonist atropine (1 mg/kg) resulted in no significant change in heart rate or arterial pressure at any developmental age. In addition, the general cardiovascular depressive effects of hypoxia were unaltered by pretreatment with atropine. In addition, the ganglionic blocking agent hexamethonium (25 mg/kg) did not induce changes in heart rate. The β-adrenergic antagonist propranolol (3 mg/kg) induced a bradycardia of similar magnitude on all days studied, with a transient hypertensive action on days 19–20, indicating the existence of an important cardiac and vascular β-adrenergic tone. Injections of the α-adrenergic antagonists prazosin or phentolamine (1 mg/kg) reduced arterial pressure significantly on all days of incubation studied. Collectively, the data indicate that embryonic chickens rely primarily on adrenergic control of cardiovascular function, with no contribution from the parasympathetic nervous system.