bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold exposure increases runningV˙o 2 max and cost of transport in goats
Authors: Schaeffer P. J. , Hokanson J. F. , Wells D. J. , Lindstedt S. L.
Published: December 2017

We inadvertently subjected a group of goats to 5 mo of cold exposure (mean minimum temperature less than −13°C) during an experiment designed to examine the effects of training by daily running on one member of each sibling pair. During the three coldest months, the sedentary but cold-exposed goats experienced a 34% increase in maximal oxygen uptake (V˙o 2 max, P < 0.01) and a 29% increase in running speed at maximal ( P < 0.05). When temperatures increased in the spring, both oxygen uptake and running speed decreased. We interpret these findings as evidence that cold is a sufficient stimulus to invoke the development of aerobic structures in muscle and that these structures subsequently can be utilized for the novel task of running. When the experiment was subsequently repeated without the cold exposure, running speed andV˙o 2 max of trained animals increased less than in either group of cold-exposed animals. However, the cost of transport of these warm runners was lower than either group of cold-exposed animals (from 13–19%, P < 0.0001). Thus, although aerobic capacity was increased with acclimation to severe winter weather, cold-acclimated goats operated with lower efficiency during locomotion.
Repeated immobilization stress reduces rat vertebral bone growth and osteocalcin
Authors: Patterson-Buckendahl Patricia , Rusnák Milan , Fukuhara Koki , Kvetnan̆ský Richard
Published: December 2017

We previously showed that psychological stressors alter plasma levels of osteocalcin (pOC), a bone-specific mineral binding protein, in ways that differ with the type of stressor. To determine effects of chronic stress, we examined vertebrae, pOC, and corticosterone levels from conscious rats subjected to foot-restraint immobilization (Immo) daily for 1–42 times. After 40–42 Immo, basal pOC was decreased by 25% compared with unstressed rats, and the subsequent rise in pOC during Immo was blunted. Corticosterone was elevated 10-fold during Immo. Immo for seven times did not change vertebral OC concentration, but caused a slight decrease in calcium and phosphorous concentrations in younger rats. Rats Immo for 42 times exhibited reduced body weight, vertebral weight, and vertebral OC concentration but no significant differences in vertebral mineral concentrations. Body fat content was visibly decreased. We do not know the source of or the stimulus for the initial rise in pOC. We conclude that both decreased growth and bone OC concentration are due to repeatedly elevated stress hormones.
[Ca2+]isignaling in renal arterial smooth muscle cells of pregnant rat is enhanced during inhibition of NOS
Authors: Murphy Jason G. , Fleming John B. , Cockrell Kathy L. , Granger Joey P. , Khalil Raouf A.
Published: December 2017

Vascular resistance and arterial pressure are reduced during normal pregnancy, but dangerously elevated during pregnancy-induced hypertension (PIH), and changes in nitric oxide (NO) synthesis have been hypothesized as one potential cause. In support of this hypothesis, chronic inhibition of NO synthesis in pregnant rats has been shown to cause significant increases in renal vascular resistance and hypertension; however, the cellular mechanisms involved are unclear. We tested the hypothesis that the pregnancy-associated changes in renal vascular resistance reflect changes in contractility and intracellular Ca2+concentration ([Ca2+]i) of renal arterial smooth muscle. Smooth muscle cells were isolated from renal interlobular arteries of virgin and pregnant Sprague-Dawley rats untreated or treated with the NO synthase inhibitor nitro-l-arginine methyl ester (l-NAME; 4 mg · kg−1· day−1for 5 days), then loaded with fura 2. In cells of virgin rats incubated in Hanks' solution (1 mM Ca2+), the basal [Ca2+]iwas 86 ± 6 nM. Phenylephrine (Phe, 10−5M) caused a transient increase in [Ca2+]ito 417 ± 11 nM and maintained an increase to 183 ± 8 nM and 32 ± 3% cell contraction. Membrane depolarization by 51 mM KCl, which stimulates Ca2+entry from the extracellular space, caused maintained increase in [Ca2+]ito 292 ± 12 nM and 31 ± 2% contraction. The maintained Phe- and KCl-induced [Ca2+]iand contractions were reduced in pregnant rats but significantly enhanced in pregnant rats treated withl-NAME. Phe- and KCl-induced contraction and [Ca2+]iwere not significantly different between untreated and l-NAME-treated virgin rats or between untreated and l-NAME + l-arginine treated pregnant rats. In Ca2+-free Hanks', application of Phe or caffeine (10 mM), to stimulate Ca2+release from the intracellular stores, caused a transient increase in [Ca2+]iand a small cell contraction that were not significantly different among the different groups. Thus renal interlobular smooth muscle of normal pregnant rats exhibits reduction in [Ca2+]isignaling that involves Ca2+entry from the extracellular space but not Ca2+release from the intracellular stores. The reduced renal smooth muscle cell contraction and [Ca2+]iin pregnant rats may explain the decreased renal vascular resistance associated with normal pregnancy, whereas the enhanced cell contraction and [Ca2+]iduring inhibition of NO synthesis in pregnant rats may, in part, explain the increased renal vascular resistance associated with PIH.
Cytoskeletal protein contents before and after hindlimb suspension in a fast and slow rat skeletal muscle
Authors: Chopard Angele , Pons Françoise , Marini Jean-François
Published: December 2017

Transversal cytoskeletal organization of muscle fibers is well described, although very few data are available concerning protein content. Measurements of desmin, α-actinin, and actin contents in soleus and extensor digitorum longus (EDL) rat skeletal muscles, taken with the results previously reported for several dystrophin-glycoprotein complex (DGC) components, indicate that the contents of most cytoskeletal proteins are higher in slow-type fibers than in fast ones. The effects of hypokinesia and unloading on the cytoskeleton were also investigated, using hindlimb suspension. First, this resulted in a decrease in contractile protein contents, only after 6 wk, in the soleus. Dystrophin and associated proteins were shown to be reduced for soleus at 3 wk, whereas only the dystrophin-associated proteins were found to increase after 6 wk. On the other hand, the contents of DGC components were increased for EDL for the two durations. Desmin and α-actinin levels were unchanged in the same conditions. Consequently, it can be concluded that the cytoskeletal protein expression levels could largely contribute to muscle fiber adaptation induced by modified functional demands.
Functional desensitization to isoproterenol without reducing cAMP production in canine failing cardiocytes
Authors: Laurent Charles-E. , Cardinal René , Rousseau Guy , Vermeulen Michel , Bouchard Caroline , Wilkinson Michael , Armour J. Andrew , Bouvier Michel
Published: December 2017

To corroborate alterations in the functional responses to β-adrenergic receptor (β-AR) stimulation with changes in β-AR signaling in failing cardiomyocytes, contractile and L-type Ca2+ current responses to isoproterenol along with stimulated cAMP generation were compared among cardiomyocytes isolated from canines with tachycardia-induced heart failure or healthy hearts. The magnitude of shortening of failing cardiomyocytes was significantly depressed (by 22 ± 4.4%) under basal conditions, and the maximal response to isoproterenol was significantly reduced (by 45 ± 18%). Similar results were obtained when the responses in the rate of contraction and rate of relaxation to isoproterenol were considered. The L-type Ca2+ current amplitude measured in failing cardiomyocytes under basal conditions was unchanged, but the responses to isoproterenol were significantly reduced compared with healthy cells. Isoproterenol-stimulated cAMP generation was similar in sarcolemmal membranes derived from the homogenates of failing (45 ± 6.8) and healthy cardiomyocytes (52 ± 8.5 pmol cAMP · mg protein−1 · min−1). However, stimulated cAMP generation was found to be significantly reduced when the membranes were derived from the homogenates of whole tissue (failing: 67 ± 8.1 vs. healthy: 140 ± 27.8 pmol cAMP · mg protein−1 · min−1). Total β-AR density was not reduced in membranes derived from either whole tissue or isolated cardiomyocyte homogenates, but the β1/β2 ratio was significantly reduced in the former (failing: 45/55 vs. healthy: 72/28) without being altered in the latter (failing: 72/28, healthy: 77/23). We thus conclude that, in tachycardia-induced heart failure, reduction in the functional responses of isolated cardiomyocytes to β-AR stimulation may be attributed to alterations in the excitation-contraction machinery rather than to limitation of cAMP generation.
Organ-specific distribution of AP-1 in AP-1 luciferase transgenic mice during the maturation process
Authors: Zhong Shu Ping , Ma Wei-Ya , Quealy James A. , Zhang Yiguo , Dong Zigang
Published: December 2017

Activator protein-1 (AP-1), a dimeric complex consisting of proteins encoded by the junand fos gene families, is a transcription factor induced by a variety of signals including those eliciting proliferation, differentiation, and neoplastic transformation. Although AP-1 has been widely studied in the last decade, physiological levels of AP-1 in different tissues are unclear. In the present study, we analyzed AP-1 activity in several organs (liver, kidney, brain, lung, spleen, heart, skin) of AP-1-luciferase transgenic mice of various ages. Results of these studies indicate that the level of AP-1 in young mice is much higher than that in older mice, and, second, that the skin contains considerably higher levels of AP-1 than other organs. The level of phosphorylated extracellular signal-regulated protein kinase (ERK) in skin was higher in 1- and 2-day-old mice than in mice of other ages. In addition, phosphorylated p38 kinase was high in 2-day-old and 1-wk-old mice, but phosphorylated c-Jun NH2-terminal kinase was not detected at any age. AP-1 activity and level of phosphorylated ERKs declined with maturation. These results imply that AP-1 activity mediated through an ERKs-dependent pathway may be involved in skin development.
Sleep changes induced by lipopolysaccharide in the rat are influenced by age
Authors: Schiffelholz Thomas , Lancel Marike
Published: December 2017

In mammals, aging is associated with immune senescense. To examine whether the sleep changes occurring during immune challenge are affected by age, we assessed sleep alterations induced by the administration of lipopolysaccharide (LPS) in young and middle-aged rats. During vehicle, the middle-aged rats exhibited less pre-rapid eye movement sleep (pre-REMS) as well as REMS, due to a smaller number and shorter duration of REMS episodes, than young rats. LPS elevated body temperature, increased non-REMS, and suppressed both pre-REMS and REMS in the young as well as in the middle-aged rats. However, in the young animals, LPS significantly enhanced slow-wave activity in the electroencephalogram (EEG) within non-REMS, reflecting an increase in sleep intensity. In contrast, LPS attenuated EEG power in most frequency bands in the older animals. This finding indicates age-related changes in the modulation of sleep by LPS.
Angiotensin-(1–7) in the ovine fetus
Authors: Moritz Karen M. , Campbell Duncan J. , Wintour E. Marelyn
Published: December 2017

In the adult animal, ANG-(1–7) may counterbalance some effects of ANG II. Its effects in the fetus are unknown. Basal ANG-(1–7), ANG I, ANG II, and renin concentrations were measured in plasma from ovine fetuses and their mothers ( n = 10) at 111 days of gestation. In the fetus, concentrations of ANG I, ANG-(1–7), and ANG II were 86 ± 21, 13 ± 2, and 14 ± 2 fmol/ml, respectively. In the ewe, concentrations of ANG I were significantly lower (20 ± 4 fmol/ml, P < 0.05) as were concentrations of ANG-(1–7) (2.9 ± 0.6 fmol/ml), whereas ANG II concentrations were not different (10 ± 1 fmol/ml). Plasma renin concentrations were higher in the fetus (4.8 ± 1.1 pmol ANG I · ml−1· h−1) than in the ewe (0.9 ± 0.2 pmol · ml−1· h−1, P < 0.05). Infusion of ANG-(1–7) (∼9 μg/h) for a 3-day period caused a significant increase in plasma concentrations of ANG-(1–7) reaching a maximum of 448 ± 146 fmol/ml on day 3 of infusion. Plasma levels of ANG I and II as well as renin were unchanged by the infusion. Urine flow rate, glomerular filtration rate, and fetal arterial blood pressure did not change and were not different than values in fetuses receiving a saline infusion for 3 days ( n = 5). However, the osmolality of amniotic and allantoic fluid was significantly higher in fetuses that received ANG-(1–7). Also, compared with the saline-infused animals, mRNA expression levels of renin, the AT1receptor, and AT2receptor were elevated in kidneys of fetuses that received infusions of ANG-(1–7). Infusion of an ANG-(1–7) antagonist {[d-Ala7]-ANG-(1–7), 20 μg/h} for 3 days had no effect on fetal blood pressure or renal function. In conclusion, although infusion of ANG-(1–7) did not affect fetal urine flow rate, glomerular filtration rate, or blood pressure, changes in fetal fluids and gene expression indicate that ANG-(1–7) may play a role in the fetal kidney.
Glutamatergic and GABAergic inputs to the RVL mediate cardiovascular adjustments to noxious stimulation
Authors: Possas Olga S. , Lopes Oswaldo U. , Cravo Sérgio L.
Published: December 2017

Stimulation of cutaneous and muscle afferents induces several cardiovascular adjustments such as hypertension, tachycardia, and muscle vasodilation. Although previous studies have demonstrated that the rostral ventrolateral medulla (RVL) mediates sympathoexcitation and pressor responses to sciatic nerve stimulation (SNS), whether it also mediates blood flow adjustments remains unclear. Therefore, in the present study, we examined the role of the RVL in the vasodilation induced by SNS and the possible neurotransmitters involved. In Urethane-anesthetized, paralyzed, and artificially ventilated rats, SNS (square pulses, 1 ms, 20 Hz, 800–1200 μA, 10 s) produced increases in blood pressure, heart rate, blood flow, and vascular conductance of the stimulated limb. Unilateral microinjection of kainic acid (2 nmol/100 nl) into the RVL contralateral to the stimulated limb abolished cardiovascular adjustments to SNS. Unilateral microinjections of kynurenic acid (2 nmol/100 nl) selectively abolished the pressor response to SNS, whereas bicuculline (400 pmol/100 nl) abolished the increases in blood flow without changing the pressor response. These results suggest that glutamatergic synapses within the RVL mediate pressor responses, whereas GABAergic synapses may mediate the vasodilation to SNS.
Physicochemical analysis of phasic menstrual cycle effects on acid-base balance
Authors: Preston Robert J. , Heenan Aaron P. , Wolfe Larry A.
Published: December 2017

In accordance with Stewart's physicochemical approach, the three independent determinants of plasma hydrogen ion concentration ([H+]) were measured at rest and during exercise in the follicular (FP) and luteal phase (LP) of the human menstrual cycle. Healthy, physically active women with similar physical characteristics were tested during either the FP ( n = 14) or LP ( n = 14). Arterialized blood samples were obtained at rest and after 5 min of upright cycling at both 70 and 110% of the ventilatory threshold (TVent). Measurements included plasma [H+], arterial carbon dioxide tension (PaCO2 ), total weak acid ([ATot]) as reflected by total protein, and the strong-ion difference ([SID]). The transition from rest to exercise in both groups resulted in a significant increase in [H+] at 70% TVentversus rest and at 110% TVent versus both rest and 70% TVent. No significant between-group differences were observed for [H+] at rest or in response to exercise. At rest in the LP, [ATot] and PaCO2 were significantly lower (acts to decrease [H+]) compared with the FP. This effect was offset by a reduction in [SID] (acts to increase [H+]). After the transition from rest to exercise, significantly lower [ATot] during the LP was again observed. Although the [SID] and PaCO2 were not significantly different between groups, trends for changes in these two variables were similar to changes in the resting state. In conclusion, mechanisms regulating [H+] exhibit phase-related differences to ensure [H+] is relatively constant regardless of progesterone-mediated ventilatory changes during the LP.
Role of PAC1 receptor in adrenal catecholamine secretion induced by PACAP and VIP in vivo
Authors: Lamouche Stéphane , Yamaguchi Nobuharu
Published: December 2017

The present study was conducted to investigate the functional implication of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I (PAC1) receptor in the adrenal catecholamine (CA) secretion induced by either PACAP-27 or vasoactive intestinal polypeptide (VIP) in anesthetized dogs. PACAP-27, VIP, and their respective antagonists were locally infused to the left adrenal gland via the left adrenolumbar artery. Plasma CA concentrations in adrenal venous and aortic blood were determined by means of a high-performance liquid chromatograph coupled with an electrochemical detector. Adrenal venous blood flow was measured by gravimetry. The administration of PACAP-27 (50 ng) resulted in a significant increase in adrenal CA output. VIP (5 μg) also increased the basal CA secretion to an extent comparable to that observed with PACAP-27. In the presence of PACAP partial sequence 6–27 [PACAP-(6–27); a PAC1 receptor antagonist] at the doses of 7.5 and 15 μg, the CA response to PACAP-27 was attenuated by ∼50 and ∼95%, respectively. Although the CA secretagogue effect of VIP was blocked by ∼85% in the presence of PACAP-(6–27) (15 μg), it remained unaffected by VIP partial sequence 10–28 [VIP-(10–28); a VIP receptor antagonist] at the dose of 15 μg. Furthermore, the CA response to PACAP-27 did not change in the presence of the same dose of VIP-(10–28). The results indicate that PACAP-(6–27) diminished, in a dose-dependent manner, the increase in adrenal CA secretion induced by PACAP-27. The results also indicate that the CA response to either PACAP-27 or VIP was selectively inhibited by PACAP-(6–27) but not by VIP-(10–28). It is concluded that PAC1receptor is primarily involved in the CA secretion induced by both PACAP-27 and VIP in the canine adrenal medulla in vivo.
Role of inferior olive and thoracic IML neurons in nonshivering thermogenesis in rats
Authors: Uno Tadashi , Shibata Masaaki
Published: December 2017

Removal of the midbrain tonic inhibitory mechanism on nonshivering thermogenesis (NST) results in increased temperatures of the interscapular brown adipose tissue (IBAT) and rectum (TIBAT and Trec, respectively) via an enhanced central sympathetic output. Because it is unlikely that neurons (primary) of the midbrain inhibitory mechanism tonically inhibit the IBAT monosynaptically, there must be secondary or tertiary neurons posterior to the midbrain. Such neurons, therefore, may increase their activity during enhanced NST after removal of the midbrain tonic inhibition. The aim of the present experiments was to localize these secondary or tertiary neurons and establish descending neuronal pathway(s) that may project to the major NST effector IBAT. TIBAT and Trec increases induced by removal of the tonic inhibition by midbrain procaine microinjections were accompanied with appearance of c-Fos-positive neurons in the inferior olive (IO) and the intermediolateral (IML) cell column of the thoracic spinal cord. Electrical stimulation of and l-glutamate microinjections into the IO increased TIBAT and Trec. Midbrain procaine-induced TIBAT and Trec increases were blocked by electrolytic IO lesions. These results suggest that central thermal signals produced from the lower midbrain are transmitted to IBAT through the IO and IML and that the IO has a role in the central sympathetic functions.
Influence of rostral ventrolateral medulla on renal sympathetic baroreflex in conscious rabbits
Authors: Mayorov Dmitry N. , Head Geoffrey A.
Published: December 2017

Previous studies with anesthetized animals have shown that the pressor region of the rostral ventrolateral medulla (RVLM) is a critical site in vasomotor control. The aim of this study was to develop, in conscious rabbits, a technique for microinjecting into the RVLM and to determine the influence of this area on renal sympathetic nerve activity (RSNA) and arterial pressure (AP) using local injections of glutamate, rilmenidine, ANG II and sarile. Rabbits were implanted with guide cannulas for bilateral microinjections into the RVLM ( n = 7) or into the intermediate ventrolateral medulla (IVLM, n = 6) and an electrode for measuring RSNA. After 7 days of recovery, injections of glutamate (10 and 20 nmol) into the RVLM increased RSNA by 81 and 88% and AP by 17 and 25 mmHg, respectively. Infusion of glutamate (2 nmol/min) into the RVLM increased AP by 15 mmHg and the RSNA baroreflex range by 38%. By contrast, injection of the imidazoline receptor agonist rilmenidine (4 nmol) into the RVLM decreased AP by 8 mmHg and the RSNA baroreflex range by 37%. Injections of rilmenidine into the IVLM did not alter AP or RSNA. Surprisingly, treatments with ANG II (4 pmol/min) or the ANG II receptor antagonist sarile (500 pmol) into the RVLM did not affect the resting or baroreflex parameters. Infusion of ANG II (4 pmol/min) into the fourth ventricle increased AP and facilitated the RSNA baroreflex. Our results show that agents administered via a novel microinjecting system for conscious rabbits can selectively modulate neuronal activity in circumscribed regions of the ventrolateral medulla. We conclude that the RVLM plays a key role in circulatory control in conscious rabbits. However, we find no evidence for the role of ANG II receptors in the RVLM in the moment-to-moment regulation of AP and RSNA.
Baroreflex effectiveness index: an additional measure of baroreflex control of heart rate in daily life
Authors: Di Rienzo Marco , Parati Gianfranco , Castiglioni Paolo , Tordi Roberto , Mancia Giuseppe , Pedotti Antonio
Published: December 2017

In healthy subjects, progressive beat-to-beat increases or decreases in systolic blood pressure (SBP) ramps are not always accompanied by baroreflex-driven lengthening or shortening in pulse interval (PI) ramps, respectively. This phenomenon has been quantified by a new index, the baroreflex effectiveness index (BEI), defined as the ratio between the number of SBP ramps followed by the respective reflex PI ramps and the total number of SBP ramps observed in a given time window. Specificity of BEI was shown in eight cats by a −89% reduction of BEI after sinoaortic denervation. In 14 healthy humans, the 24-h average BEI value was 0.21, with a marked day-night modulation (≈0.25 day, ≈0.15 night) in counterphase with modulation of baroreflex sensitivity (BRS). Our analysis indicates that 1) in normal subjects, arterial baroreflex can induce beat-by-beat PI changes in response to only 21% of all SBP ramps, possibly because of central inhibitory influences or of interferences at sinus node level by nonbaroreflex mechanisms and 2) BEI provides information on the baroreflex function that is complementary to BRS.
Oxytocin antagonist disrupts hypotension-evoked renin secretion and other responses in conscious rats
Authors: Huang Wan , Sjöquist Mats , Skott Ole , Stricker Edward M. , Sved Alan F.
Published: December 2017

Previous experiments have indicated that arterial hypotension increases plasma oxytocin (OT) levels in rats and that OT infused intravenously causes an increase in plasma renin activity (PRA). The goal of the present study was to determine whether systemic administration of an OT receptor antagonist would attenuate the increase in PRA that is normally evoked by arterial hypotension in rats. In conscious male rats, intravenous injection of hydralazine or diazoxide produced sustained hypotension and evoked a significant increase in PRA, as expected. Intravenous infusion of an OT receptor antagonist did not alter the hypotension induced by hydralazine or diazoxide, but it did markedly blunt the induced increase in PRA. The OT receptor antagonist also blunted the hypotension-evoked increase in heart rate and plasma vasopressin levels, suggesting that the antagonist may have generally disrupted afferent signaling of hypotension. Thus hypotension-evoked OT secretion may contribute to cardiovascular homeostasis by enhancing baroreceptor signals that stimulate increases in renin secretion, vasopressin secretion, and heart rate during arterial hypotension in rats.
Dual effect of HBO on cerebral infarction in MCAO rats
Authors: Badr A. E. , Yin W. , Mychaskiw G. , Zhang J. H.
Published: December 2017

Various reports in the literature have shown that hyperbaric oxygen (HBO) reduces cerebral infarction both in animals and humans. After the initial ischemic insult, however, initiating HBO treatment at different intervals has yielded conflicting results. The present study was undertaken to determine the optimal therapeutic window in which to start HBO treatment for cerebral infarction after transient focal ischemia. In this study, the operator occluded the middle cerebral artery (MCA) of anesthetized rats by introducing a blunted nylon filament into the proximal MCA from the dissected external carotid artery. When the operator removed the filament after 2 h, focal ischemia and reperfusion occurred. The operator then placed the rat in the HBO chamber and administered 3 atm absolute HBO for 1 h according to the protocol. The rat was killed 24 h after reperfusion, and the percentage of infarction (infarct ratio) was calculated by dividing the infarction area by the total area of the ipsilateral hemisphere. The results showed that the percentage of infarcted area decreased significantly ( P < 0.05) both in the 3- (7.59%) and 6-h (5.35%) HBO-treatment groups compared with the control (no treatment) group (11.34%). However, the percentage of infarcted area increased significantly ( P< 0.01 and P < 0.05, respectively) both in the 12- (23%) and 23-h (20%) treatment groups. The results of this study suggest that applying HBO within 6 h of ischemia-reperfusion injury could benefit the patient but that applying HBO 12 h or more after injury could harm the patient.
Effects of prolonged fasting on plasma cortisol and TH in postweaned northern elephant seal pups
Authors: Ortiz Rudy M. , Wade Charles E. , Ortiz C. Leo
Published: December 2017

Northern elephant seal ( Mirounga angustirostris) pups rely on the oxidation of fat stores as their primary source of energy during their 8- to 12-wk postweaning fast; however, potential endocrine mechanisms involved with this increased fat metabolism have yet to be examined. Therefore, 15 pups were serially blood sampled in the field during the first 7 wk of their postweaning fast to examine the changes in plasma concentrations of cortisol and thyroid hormones (TH), which are involved in fat metabolism in other mammals. Cortisol increased, indicating that it contributed to an increase in lipolysis. Increased total triiodothyronine (tT3) and thyroxine (tT4) may not reflect increased thyroid gland activity, but rather alterations in hormone metabolism. tT3-to-tT4ratio decreased, suggesting a decrease in thyroxine (T4) deiodination, whereas the negative correlation between total proteins and free T4suggests that the increase in free hormone is attributed to a decrease in binding globulins. Changes in TH are most similar to those observed during hibernation than starvation in mammals, suggesting that the metabolic adaptations to natural fasting are more similar to hibernation despite the fact these animals remain active throughout the fasting period.
Plasma copper clearance and biliary copper excretion are stimulated in copper-acclimated trout
Authors: Grosell M. , McGeer J. C. , Wood C. M.
Published: December 2017

Nonacclimated and Cu-acclimated rainbow trout ( Oncorhynchus mykiss) exhibited equally rapid clearance of a single bolus of injected64Cu (3,780 nmol/kg) from the plasma (32–40 min to half- concentration). Eight hours after Cu injection, ∼80% of the injected Cu was found in the liver. However, when Cu labeled with64Cu was presented intravascularly via continuous infusion at a rate of 158 nmol · kg−1· h−1for 72 h, Cu-acclimated fish cleared plasma Cu more effectively than nonacclimated fish. The use of chronically implanted cystic bile duct cannulas revealed a fourfold increase in hepatobiliary Cu excretion in Cu-acclimated fish during infusion, demonstrating the important homeostatic role of the liver in Cu metabolism. Extrahepatobiliary Cu excretion, likely through the gills and apparently exceeding biliary Cu excretion, was evident from appearance of64Cu in the ambient water but was not altered by Cu acclimation. Cu accumulation in white muscle also played an important a role in copper homeostasis.
Effects of converting enzyme inhibitors on renalP-450 metabolism of arachidonic acid
Authors: Ito Osamu , Omata Ken , Ito Sadayoshi , Hoagland Kimberly M. , Roman Richard J.
Published: December 2017

The effects of blockade of the renin-angiotensin system on the renal metabolism of arachidonic acid (AA) were examined. Male Sprague-Dawley rats were treated with vehicle, captopril (25 mg · kg−1· day−1), enalapril (10 mg · kg−1· day−1), or candesartan (1 mg · kg−1· day−1) for 1 wk. The production of 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) by renal cortical microsomes increased in rats treated with captopril by 59 and 24% and by 90 and 58% in rats treated with enalapril. Captopril and enalapril increased 20-HETE production in the outer medulla by 100 and 143%, respectively. In contrast, blockade of ANG II type 1 receptors with candesartan had no effect on the renal metabolism of AA. Captopril and enalapril increased cytochrome P-450 (CYP450) reductase protein levels in the renal cortex and outer medulla and the expression of CYP450 4A protein in the outer medulla. The effects of captopril on the renal metabolism of AA were prevented by the bradykinin-receptor antagonist, HOE-140, or the nitric oxide (NO) synthase inhibitor, NG-nitro-l-arginine methyl ester. These results suggest that angiotensin-converting enzyme inhibitors may increase the formation of 20-HETE and EETs secondary to increases in the intrarenal levels of kinins and NO.
Osmoregulation in water-deprived rats drinking hypertonic saline: effect of area postrema lesions
Authors: Stricker Edward M. , Craver Carl F. , Curtis Kathleen S. , Peacock-Kinzig Kimberly A. , Sved Alan F. , Smith James C.
Published: December 2017

Rats drank rapidly when 0.3 M NaCl was the only drinking fluid available after overnight water deprivation, consuming ∼200 ml/24 h. Although such large intakes of this hypertonic solution initially elevated plasma osmolality, excretion of comparable volumes of urine more concentrated than 300 meq Na+/l ultimately appears to restore plasma osmolality to normal levels. Rats drank ∼100 ml of 0.5 M NaCl after overnight water deprivation, but urine Na+ concentration (UNa) did not increase sufficiently to achieve osmoregulation. When an injected salt load exacerbated the initial dehydration caused by water deprivation, rats increased UNa to void the injected load and did not significantly alter 24-h intake of 0.3 or 0.5 M NaCl. Rats with lesions of area postrema had much higher saline intakes and lower UNa than did intact control rats; nonetheless, they appeared to osmoregulate well while drinking 0.3 M NaCl but not while drinking 0.5 M NaCl. Detailed analyses of drinking behavior by intact rats suggest that individual bouts were terminated by some rapid postabsorptive consequence of the ingested NaCl load that inhibited further NaCl intake, not by a fixed intake volume or number of licks that temporarily satiated thirst.
Effects of the β2-agonist clenbuterol on respiratory and limb muscles of weaning rats
Authors: Polla B. , Cappelli V. , Morello F. , Pellegrino M. A. , Boschi F. , Pastoris O. , Reggiani C.
Published: December 2017

The aim of this study was to analyze the effects of chronic administration of the β2-agonist clenbuterol (1.5 mg · kg−1· day−1for 4 wk in the drinking water) on respiratory (diaphragm and parasternal intercostal) and hindlimb (tibialis and soleus) muscles in young rats during postnatal development (21 to 49 postnatal days).

The treatment resulted in very little stimulation of muscle growth. Significant slow-to-fast transitions in the expression of myosin heavy chain isoforms and significant increases in the myofibrillar ATPase activity were found in the diaphragm and soleus, whereas tibialis anterior and intercostal muscles did not show any significant fiber-type alteration. Decrease of oxidative enzyme activities and increase of glycolytic enzyme activities were also observed.

It is concluded that whereas the growth stimulation is age dependent and only detectable in adult rats, the fiber-type transformation is also present in weaning rats and particularly evident in the soleus and diaphragm. The fiber-type transformation caused by clenbuterol might lead to an enhancement of contractile performance and also to a reduced resistance to fatigue.
Upregulation of G protein-linked receptor kinases with advancing age in rat aorta
Authors: Schutzer William E. , Reed John F. , Bliziotes Michael , Mader Scott L.
Published: December 2017

The age-related decline in β-adrenergic receptor (β-AR)-mediated vasorelaxation is associated with desensitization of β-ARs without significant downregulation. The primary mode of this homologous β-AR desensitization, in general, is via G protein receptor kinases (GRK). Therefore, we hypothesize that age-related changes in GRKs are causative to this etiology in rat aorta. Herein, we investigate the activity and cellular distribution (cytoplasmic vs. membrane) of several GRK isoforms and β-arrestin proteins. GRK activity was assessed in extracts from aortic tissue of 6-wk, 6-mo, 12-mo, and 24-mo-old male Fischer-344 rats using a rhodopsin phosphorylation assay. We also performed immunoblots on lysates from aorta with specific antibodies to GRK-2, -3, -5, and β-arrestin-1. Results show an age-related increase in GRK activity. Furthermore, expression of GRK-2 (cytoplasmic and membrane), GRK-3 (cytoplasmic and membrane), and β-arrestin (soluble) increased with advancing age, whereas GRK-5 (membrane) expression remained unchanged. These results suggest that age is associated with increased activity and expression of specific GRKs. This increase likely results in enhanced phosphorylation and desensitization of β-ARs. These biochemical changes are consistent with observed aging physiology.
CLA reduces antigen-induced histamine and PGE2release from sensitized guinea pig tracheae
Authors: Whigham Leah D. , Cook Ellen B. , Stahl James L. , Saban Ricardo , Bjorling Dale E. , Pariza Michael W. , Cook Mark E.
Published: December 2017

Conjugated linoleic acid (CLA) has been shown to enhance immune reactions such as lymphocyte blastogenesis and delayed-type hypersensitivity. We investigated the role of CLA in type I (immediate) hypersensitivity, using a guinea pig tracheal superfusion model for measuring antigen-induced airway smooth muscle contraction and inflammatory mediator release. Female Hartley guinea pigs were fed a diet supplemented with 0.25 g corn oil or linoleic acid/100 g of diet (control) or 0.25 g CLA/100 g of diet for at least 1 wk before and during active sensitization to ovalbumin antigen. Tracheae from sensitized guinea pigs were suspended in air-filled water-jacketed (37°C) tissue chambers in a superfusion apparatus. Tracheae were superfused with buffer containing antigen, and tissue contraction was recorded. Superfusate was collected at 90-s intervals for evaluation of histamine and PGE2release. CLA did not affect antigen-induced tracheal contractions when expressed as gram contraction per gram tissue. CLA significantly reduced antigen-induced histamine and PGE2release. CLA appears to decrease release of some inflammatory mediators during type I hypersensitivity reactions.
Cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in obese Zucker rats
Authors: Overton J. M. , Williams T. D. , Chambers J. B. , Rashotte M. E.
Published: December 2017

The primary purpose of the study was to test the hypothesis that reduced leptin signaling is necessary to elicit the cardiovascular and metabolic responses to fasting. Lean ( Fa/?; normal leptin receptor; n = 7) and obese ( fa/fa; mutated leptin receptor; n = 8) Zucker rats were instrumented with telemetry transmitters and housed in metabolic chambers at 23°C (12:12-h light-dark cycle) for continuous (24 h) measurement of metabolic and cardiovascular variables. Before fasting, mean arterial pressure (MAP) was higher (MAP: obese = 103 ± 3; lean = 94 ± 1 mmHg), whereas oxygen consumption (V˙o2: obese = 16.5 ± 0.3; lean = 18.6 ± 0.2 ml · min−1· kg−0.75) was lower in obese Zucker rats compared with their lean controls. Two days of fasting had no effect on MAP in either lean or obese Zucker rats, whereas V˙o2(obese = −3.1 ± 0.3; lean = −2.9 ± 0.1 ml · min−1· kg−0.75) and heart rate (HR: obese = −56 ± 4; lean = −42 ± 4 beats/min) were decreased markedly in both groups. Fasting increased HR variability both in lean (+1.8 ± 0.4 ms) and obese (+2.6 ± 0.3 ms) Zucker rats. After a 6-day period of ad libitum refeeding, when all parameters had returned to near baseline levels, the cardiovascular and metabolic responses to 2 days of thermoneutrality (ambient temperature 29°C) were determined. Thermoneutrality reduced V˙o2(obese = −2.4 ± 0.2; lean = −3.3 ± 0.2 ml · min−1· kg−0.75), HR (obese = −46 ± 5; lean = −55 ± 4 beats/min), and MAP (obese = −13 ± 6; lean = −10 ± 1 mmHg) similarly in lean and obese Zucker rats. The results indicate that the cardiovascular and metabolic responses to fasting and thermoneutrality are conserved in Zucker rats and suggest that intact leptin signaling may not be requisite for the metabolic and cardiovascular responses to reduced energy intake.
NO supports right ventricular flow dominance and whole body O2 utilization in midgestation fetal lambs
Authors: Smolich Joseph J.
Published: December 2017

It is unknown if nitric oxide (NO) modulates the relative levels of left (LV) and right (RV) ventricular output, fetal O2 consumption, or blood flow distribution between the body and placenta at midgestation. To address these questions, six fetal lambs were instrumented at 89–96 days gestation (term 147 days), and blood flows were measured with radioactive microspheres 3–4 days later at baseline and after inhibition of NO synthesis with 10 mg/kg (l-NNA10) and 25 mg/kg (l-NNA25) N ω-nitro-l-arginine. LV output fell by 74 ± 15 ml · min−1 · kg−1 atl-NNA10 ( P < 0.005), whereas RV output decreased by 90 ± 18 ml · min−1 · kg−1 atl-NNA10 ( P < 0.02) and by a further 80 ± 22 ml · min−1 · kg−1 atl-NNA25 ( P < 0.05). As a result, RV output exceeded LV output at baseline ( P = 0.03) and l-NNA10 ( P < 0.02) but not at l-NNA25. Fetal body blood flow fell by 95 ± 25 ml · min−1 · kg−1 atl-NNA10 ( P < 0.01), but because placental blood flow decreased by 70 ± 22 ml · min−1 · kg−1 atl-NNA10 ( P < 0.01) and a further 71 ± 21 ml · min−1 · kg−1 atl-NNA25 ( P < 0.01), the fetal body-to-placental blood flow ratio was near unity at baseline andl-NNA10 but rose to 1.5 ± 0.3 atl-NNA25 ( P < 0.05). In association with these flow changes, fetal O2 consumption declined by 1.4 ± 0.3 ml · min−1 · kg−1 atl-NNA10 ( P < 0.05) and by a further 1.5 ± 0.6 ml · min−1 · kg−1 atl-NNA25 ( P < 0.02). These findings suggest that, in midgestation fetal lambs, NO supports an RV flow dominance, whole body O2 utilization, and the maintenance of a near-equal fetoplacental blood flow distribution.
Slow oscillations in blood pressure via a nonlinear feedback model
Authors: Ringwood John V. , Malpas Simon C.
Published: December 2017

Blood pressure is well established to contain a potential oscillation between 0.1 and 0.4 Hz, which is proposed to reflect resonant feedback in the baroreflex loop. A linear feedback model, comprising delay and lag terms for the vasculature, and a linear proportional derivative controller have been proposed to account for the 0.4-Hz oscillation in blood pressure in rats. However, although this model can produce oscillations at the required frequency, some strict relationships between the controller and vasculature parameters must be true for the oscillations to be stable. We developed a nonlinear model, containing an amplitude-limiting nonlinearity that allows for similar oscillations under a very mild set of assumptions. Models constructed from arterial pressure and sympathetic nerve activity recordings obtained from conscious rabbits under resting conditions suggest that the nonlinearity in the feedback loop is not contained within the vasculature, but rather is confined to the central nervous system. The advantage of the model is that it provides for sustained stable oscillations under a wide variety of situations even where gain at various points along the feedback loop may be altered, a situation that is not possible with a linear feedback model. Our model shows how variations in some of the nonlinearity characteristics can account for growth or decay in the oscillations and situations where the oscillations can disappear altogether. Such variations are shown to accord well with observed experimental data. Additionally, using a nonlinear feedback model, it is straightforward to show that the variation in frequency of the oscillations in blood pressure in rats (0.4 Hz), rabbits (0.3 Hz), and humans (0.1 Hz) is primarily due to scaling effects of conduction times between species.
The functional regeneration of syncytiotrophoblast in cultured explants of term placenta
Authors: Simán C. M. , Sibley C. P. , Jones C. J. P. , Turner M. A. , Greenwood S. L.
Published: December 2017

We have investigated the functional characteristics of term human placental villous explants kept in long-term (7–11 days) culture. Fragments of placental villous tissue (∼5–10 mg wet wt) were cultured in supplemented CMRL-1066 culture medium for up to 11 days. After the first day of culture, the syncytiotrophoblast appeared vacuolated and eventually degenerated. However, a new syncytiotrophoblast developed by day 4, being indistinguishable from that of a fresh placenta by 11 days. Release of human chorionic gonadotrophin increased and activity of lactate dehydrogenase in culture medium decreased with culture time. Transport variables were measured over the first 7 days of culture. Basal86Rb efflux was reduced with time in culture and was inhibited by Ba2+, suggesting the efflux was mediated by K+ channels. At all stages of culture, 86Rb efflux was stimulated by ATP, hyposmotic medium, and ANG II. A complex pattern of efflux changes with culture time and type of stimulator was observed, suggesting that several compartments of the tissue contributed to stimulated efflux. This culture system provides opportunities for studies of chronic regulation of placental function.
Loxiglumide, a CCK-A receptor antagonist, stimulates calorie intake and hunger feelings in humans
Authors: Beglinger Christoph , Degen Lukas , Matzinger Daniel , D'Amato Massimo , Drewe Jürgen
Published: December 2017

Exogenous cholecystokinin (CCK) induces early satiety when infused into humans. Whether alimentary CCK (CCK-A) receptor blockade stimulates food intake in humans is, however, uncertain. The aim of the present investigation was, therefore, to establish the effect of CCK-A receptor blockade on satiety and eating behavior in healthy volunteers. To further explore the role of endogenous CCK, the effects of the specific CCK-A receptor antagonist loxiglumide (Lox; 22 μmol · kg−1· h−1) on satiety and eating behavior were investigated in healthy men and compared with saline infusions (as placebo) in a series of randomized, double-blind, placebo-controlled, crossover studies. Lox produced a slight (7%), but not significant ( P = 0.104), increase in food intake that was accompanied by a modest (10%), but significant ( P < 0.004), increase in calorie intake. Fluid ingestion was not affected by Lox. Subjects experienced more hunger and delayed fullness during Lox infusion than during saline infusion ( P < 0.05). This study provides further evidence that CCK is an endogenous physiological satiety signal acting through CCK-A receptor-mediated mechanisms. Repeated-dose studies comparing hunger and satiety responses after CCK-A receptor blockade in healthy subjects and patients with eating disorders may help clarify the possible involvement of endogenous CCK in these conditions.
Enhanced central response to dehydration in mice lacking angiotensin AT1areceptors
Authors: Morris Mariana , Means Shelia , Oliverio Michael I. , Coffman Thomas M.
Published: December 2017

The objective was to determine the central nervous system (CNS) responses to dehydration (c-Fos and vasopressin mRNA) in mice lacking the ANG AT1areceptor [ANG AT1aknockout (KO)]. Control and AT1aKO mice were dehydrated for 24 or 48 h. Baseline plasma vasopressin (VP) was not different between the groups; however, the response to dehydration was attenuated in AT1aKO (24 ± 11 vs. 10.6 ± 2.7 pg/ml). Dehydration produced similar increases in plasma osmolality and depletion of posterior pituitary VP content. Neuronal activation was observed as increases in c-Fos protein and VP mRNA. The supraoptic responses were not different between groups. In the paraventricular nucleus (PVN), c-Fos-positive neurons (57.4 ± 10.7 vs. 98.4 ± 7.4 c-Fos cells/PVN, control vs. AT1aKO) and VP mRNA levels (1.0 ± 0.1 vs. 1.4 ± 0.1 μCi, control vs. AT1aKO) were increased with greater responses in AT1aKO. A comparison of 1- to 2-day water deprivation showed that plasma VP, brain c-Fos, and VP mRNA returned toward control on day 2, although plasma osmolality remained high. Data demonstrate that AT1aKO mice show a dichotomous response to dehydration, reduced for plasma VP and enhanced for PVN c-Fos protein and VP mRNA. The results illustrate the importance of ANG AT1areceptors in the regulation of osmotic and endocrine balance.
Control of vascular tone in notothenioid fishes is determined by phylogeny, not environmental temperature
Authors: Egginton S. , Forster M. E. , Davison W.
Published: December 2017

We examined potential vasomotor control mechanisms in an Antarctic fish ( Trematomus bernacchii; usual core temperature approximately −1°C), comparing sensitivity to agonists by means of the cumulative dose response and potency with reference to depolarization by 50 mM KCl. In efferent branchial arteries, norepinephrine (NE) produced ∼20% of the maximal KCl tension and ∼40% in the presence of 10−3M sotalol, suggesting a modest contribution of α- and β-adrenergic tonus [half-maximal response (pEC50) = 6.29 ± 0.37 M]. Carbachol (CBC) and serotonin (5-HT) had different sensitivities (pEC50= 4.50 ± 0.40 and 6.82 ± 0.08 M, respectively) but similar potencies (21.6 ± 11.1 and 31.1 ± 5.3% of KCl). A related species from warmer waters around New Zealand, Paranotothenia angustata, had similar vascular reactivity for NE (pEC50= 5.48 ± 0.31 M), CBC (pEC50= 4.94 ± 0.22 M), and methysergide-sensitive vasoconstriction with 5-HT (pEC50= 6.22 ± 0.40 M). Agonist potencies were 9, 65, and 45% that of KCl, respectively. Bovichtus variegatus, a member of the phylogenetic sister group to the notothenioids, also gave broadly similar responses. In contrast, Dissostichus mawsoni, a pelagic Antarctic notothenioid, showed a dominance of vasodilatation over vasoconstriction, with sensitive isoprenaline (pEC50= 6.66 ± 0.05 M) but weak serotonergic (5.2 ± 1.5% KCl) responses. The unusual dominance of serotonergic control appears to be primarily a consequence of evolutionary lineage rather than low environmental temperature, but the pattern may be modified according to functional demand.