bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactive effects of central leptin and peripheral fuel oxidation on estrous cyclicity
Authors: Schneider Jill E. , Zhou Dan
Published: December 2017

A 48-h period of fasting inhibits estrous cycles in Syrian hamsters, and fasting-induced anestrus can be prevented by intracerebroventricular treatment with leptin during the fasting period. In the present experiment, the effects of intracerebroventricular leptin were blocked by systemic treatment with inhibitors of metabolic fuel oxidation. Leptin was infused continuously into the lateral ventricles (1 μg/day) during fasting on days 1 and 2 of the estrous cycle. Intraperitoneal injection of 2-deoxy-d-glucose (2DG) was used to block both central and peripheral glucose oxidation, and intragastric treatment with methyl palmoxirate (MP) was used to inhibit peripheral long-chain fatty acid oxidation during the fasting and leptin-treatment period. 2DG or MP were administered at doses that did not induce anestrus in ad libitum-fed hamsters. Despite elevated central levels of leptin, fasting-induced anestrus occurred in hamsters treated with either 2DG or MP. Thus an elevated intracerebroventricular leptin concentration is not a sufficient condition for normal estrous cycles when fuel oxidation is inhibited. These results raise the possibility that central leptin influences reproduction by indirect effects on peripheral fuel metabolism.
Nociceptin modulates renal sympathetic nerve activity through a central action in conscious rats
Authors: Shirasaka Tetsuro , Kunitake Takato , Kato Kazuo , Takasaki Mayumi , Kannan Hiroshi
Published: December 2017

Nociceptin, an endogenous agonist of the opioid receptor-like1 receptor, is expressed in the hypothalamus, where it is implicated in autonomic nervous system control. However, the central actions of nociceptin on sympathetic nerve activity have not been studied. We investigated the effect of intracerebroventricularly administered nociceptin (2–10 nmol) on blood pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious rats and sinoaortic-denervated (SAD) rats. Intracerebroventricularly administered nociceptin resulted in a dose-dependent decrease in mean arterial pressure (MAP) and HR in intact rats. RSNA decreased 31.5 ± 2.1 and 19.9 ± 5.0% at a dose of 2 and 5 nmol, respectively. In SAD rats, MAP, HR, and RSNA decreased in a dose-dependent manner, and the maximum responses were larger than those in intact rats. The decrease in HR induced by nociceptin was blocked by propranolol but not by atropine, which indicates that nociceptin is acting by inhibiting cardiac sympathetic outflow. These nociceptin-induced depressor and bradycardic responses were not antagonized by pretreatment with naloxone and nocistatin. These findings suggest that central nociceptin may have a functional role in regulating cardiovascular and sympathetic nervous systems.
Role of cholinergic receptors in adrenal catecholamine secretion in spontaneously hypertensive rats
Authors: Nagayama Takahiro , Matsumoto Takayuki , Yoshida Makoto , Suzuki-Kusaba Mizue , Hisa Hiroaki , Kimura Tomohiko , Satoh Susumu
Published: December 2017

We investigated the role of nicotinic and muscarinic receptors in secretion of catecholamines induced by transmural electrical stimulation (ES) from isolated perfused adrenal glands of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. ES (1–10 Hz) produced frequency-dependent increases in epinephrine (Epi) and norepinephrine (NE) output as measured in perfusate. The ES-induced increases in NE output, but not Epi output, were significantly greater in adrenal glands of SHRs than in those of WKY rats. Hexamethonium (10–100 μM) markedly inhibited the ES-induced increases in Epi and NE output from adrenal glands of SHRs and WKY rats. Atropine (0.3–3 μM) inhibited the ES-induced increases in Epi and NE output from adrenal glands of SHRs, but not from those of WKY rats. These results suggest that endogenous acetylcholine-induced secretion of adrenal catecholamines is predominantly mediated by nicotinic receptors in SHRs and WKY rats and that the contribution of muscarinic receptors may be different between these two strains.
Contributions of MSNA and stroke volume to orthostatic intolerance following bed rest
Authors: Shoemaker J. K. , Hogeman C. S. , Sinoway L. I.
Published: December 2017

We examined whether the altered orthostatic tolerance following 14 days of head-down tilt bed rest (HDBR) was related to inadequate sympathetic outflow or to excessive reductions in cardiac output during a 10- to 15-min head-up tilt (HUT) test. Heart rate, blood pressure (BP, Finapres), muscle sympathetic nerve activity (MSNA, microneurography), and stroke volume blood velocity (SVV, Doppler ultrasound) were assessed during supine 30° (5 min) and 60° (5–10 min) HUT positions in 15 individuals who successfully completed the pre-HDBR test without evidence of orthostatic intolerance. Subjects were classified as being orthostatically tolerant (OT, n = 9) or intolerant (OI, n = 6) following the post-HDBR test. MSNA, BP, and SVV during supine and HUT postures were not altered in the OT group. Hypotension during 60° HUT in the post-bed rest test for the OI group ( P < 0.05) was associated with a blunted increase in MSNA ( P < 0.05). SVV was reduced following HDBR in the OI group (main effect of HDBR, P < 0.02). The data support the hypothesis that bed rest-induced orthostatic intolerance is related to an inadequate increase in sympathetic discharge that cannot compensate for a greater postural reduction in stroke volume.
Seasonal changes of human circadian rhythms in Antarctica
Authors: Yoneyama S. , Hashimoto S. , Honma K.
Published: December 2017

The human circadian rhythms in sleep, activity, plasma melatonin, and rectal temperature were explored under two conflicting time cues in Antarctica: an extreme photoperiod and a strict work schedule. The nine healthy male subjects stayed at the Antarctic zone (latitude 66.5–90° south) for 15 mo including a 13-mo wintering at the Dome station (latitude 77° south). Neither the phases nor the amounts of sleep and daily activity underwent a seasonal change. On the other hand, the peak phase of melatonin rhythm was phase delayed by 4.1 h in winter compared with summer. When the analysis is limited to the Dome data, the seasonal difference was reduced to 1.3 h. Similarly the trough phase of rectal temperature rhythm in two of three subjects was phase delayed by ∼2 h in winter. From these findings, the sleep or activity rhythm is concluded to be reset predominantly by the work schedule, whereas the circadian rhythm in plasma melatonin and rectal temperature is substantially influenced by the photoperiod.
Characterization ofcis-elements required for osmotic response of rat Na+/H+exchanger-2 (NHE-2) gene
Authors: Bai Liqun , Collins James F. , Muller Yunhua L. , Xu Hua , Kiela Pawel R. , Ghishan Fayez K.
Published: December 2017

The Na+/H+exchanger ( NHE-2) has been implicated in osmoregulation in the kidney, because it transports Na+across the cell membrane and efficiently alters intracellular osmolarity. On hyperosmotic stress, NHE-2 mRNA increases in abundance in mouse inner medullary collecting duct (mIMCD-3) cells, suggesting possible transcriptional regulation. To investigate the molecular mechanism of potential transcriptional regulation of NHE-2 by hyperosmolarity, we have functionally characterized the 5′-flanking region of the gene in mIMCD-3 cells. Transient transfection of luciferase reporter gene constructs revealed a novel cis-acting element, which we call OsmoE (osmotic-responsive element, bp −808 to −791, GGGCCAGTTGGCGCTGGG), and a TonE-like element (tonicity-responsive element, bp −1201 to −1189, GCTGGAAAACCGA), which together are shown to be responsible for hyperosmotic induction of the NHE-2gene. Electrophoretic mobility shift assays suggest that different DNA-protein interactions occur between these two osmotic response elements. However, both DNA sequences were shown to specifically bind nuclear proteins that dramatically increase in abundance under hyperosmotic conditions. Isolation of trans-acting factors and characterization of their specific interaction with these osmotic response elements will further elucidate the transcriptional mechanisms controlling NHE-2 gene expression under hyperosmolar conditions.
Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day
Authors: Wyatt James K. , Cecco Angela Ritz-De , Czeisler Charles A. , Dijk Derk-Jan
Published: December 2017

The interaction of homeostatic and circadian processes in the regulation of waking neurobehavioral functions and sleep was studied in six healthy young subjects. Subjects were scheduled to 15–24 repetitions of a 20-h rest/activity cycle, resulting in desynchrony between the sleep-wake cycle and the circadian rhythms of body temperature and melatonin. The circadian components of cognitive throughput, short-term memory, alertness, psychomotor vigilance, and sleep disruption were at peak levels near the temperature maximum, shortly before melatonin secretion onset. These measures exhibited their circadian nadir at or shortly after the temperature minimum, which in turn was shortly after the melatonin maximum. Neurobehavioral measures showed impairment toward the end of the 13-h 20-min scheduled wake episodes. This wake-dependent deterioration of neurobehavioral functions can be offset by the circadian drive for wakefulness, which peaks in the latter half of the habitual waking day during entrainment. The data demonstrate the exquisite sensitivity of many neurobehavioral functions to circadian phase and the accumulation of homeostatic drive for sleep.
Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3
Authors: Clancy J. S. , Takeshima H. , Hamilton S. L. , Reid M. B.
Published: December 2017

Skeletal muscle expresses at least two isoforms of the calcium release channel in the sarcoplasmic reticulum (RyR1 and RyR3). Whereas the function of RyR1 is well defined, the physiological significance of RyR3 is unclear. Some authors have suggested that RyR3 participates in excitation-contraction coupling and that RyR3 may specifically confer resistance to fatigue. To test this hypothesis, we measured contractile function of diaphragm strips from adult RyR3-deficient mice (exon 2-targeted mutation) and their heterozygous and wild-type littermates. In unfatigued diaphragm, there were no differences in isometric contractile properties (twitch characteristics, force-frequency relationships, maximal force) among the three groups. Our fatigue protocol (30 Hz, 0.25 duty cycle, 37°C) depressed force to 25% of the initial force; however, lack of RyR3 did not accelerate the decline in force production. The force-frequency relationship was shifted to higher frequencies and was depressed in fatigued diaphragm; lack of RyR3 did not exaggerate these changes. We therefore provide evidence that RyR3 deficiency does not alter contractile function of adult muscle before, during, or after fatigue.
Glucose and fatty acid metabolism in the isolated working mouse heart
Authors: Belke Darrell D. , Larsen Terje S. , Lopaschuk Gary D. , Severson David L.
Published: December 2017

Although isolated perfused mouse heart models have been developed to study mechanical function, energy substrate metabolism has not been examined despite the expectation that the metabolic rate for a heart from a small mammal should be increased. Consequently, glucose utilization (glycolysis, oxidation) and fatty acid oxidation were measured in isolated working mouse hearts perfused with radiolabeled substrates, 11 mM glucose, and either 0.4 or 1.2 mM palmitate. Heart rate, coronary flow, cardiac output, and cardiac power did not differ significantly between hearts perfused at 0.4 or 1.2 mM palmitate. Although the absolute values obtained for glycolysis and glucose oxidation and fatty acid oxidation are significantly higher than those reported for rat hearts, the pattern of substrate metabolism in mouse hearts is similar to that observed in hearts from larger mammals. The metabolism of mouse hearts can be altered by fatty acid concentration in a manner similar to that observed in larger animals; increasing palmitate concentration altered the balance of substrate metabolism to increase overall energy derived from fatty acids from 64 to 92%.
Effect of glucose supply on ovine uteroplacental glucose metabolism
Authors: Aldoretta Peter W. , Hay William W.
Published: December 2017

To test the hypothesis that glucose supply to the uteroplacenta (UP) regulates UP glucose metabolism into oxidative and nonoxidative pathways, we studied eight late-gestation pregnant sheep at low (LG) and high (HG) maternal glucose concentrations (GM), using Fick principle and tracer glucose methodology. UP glucose consumption (UPGC) correlated directly with GM( r = 0.75, P = 0.0006), and UP glucose decarboxylation ( r = 0.80, P = 0.0001), and lactate production ( r = 0.90, P = 0.0001) rates were directly correlated with UPGC. The combined fractional production rate for lactate, fructose, and CO2 from UPGC was the same in LG and HG periods. The fraction of UP oxygen consumption used for glucose oxidation increased by about 50% from LG to HG conditions; however, there was no change in UP oxygen consumption. Nearly half of UPGC was not accounted for by lactate, fructose, and CO2 production, and about two-thirds of UP oxygen consumption was not accounted for by immediate oxidation of glucose carbon just taken up by the UP. These results indicate that glucose supply directly regulates UP glucose oxidative metabolism and that there is a reciprocal relationship between UP glucose oxidation and the oxidation of other substrates.
Heat stress induces ultrastructural changes in cutaneous capillary wall of heat-acclimated rock pigeon
Authors: Arieli Yehuda , Feinstein Neomi , Raber Pnina , Horowitz Michal , Marder Jacob
Published: December 2017

In heat-acclimated rock pigeons, cutaneous water evaporation is the major cooling mechanism when exposed at rest to an extremely hot environment of 50–60°C. This evaporative pathway is also activated in room temperature by a β-adrenergic antagonist (propranolol) or an α-adrenergic agonist (clonidine) and inhibited by a β-adrenergic agonist (isoproterenol). In contrast, neither heat exposure nor drug administration activates cutaneous evaporation in cold-acclimated pigeons. To elucidate the mechanisms underlying this phenomenon, we studied the role of the ultrastructure and permeability of the cutaneous vasculature. During both heat stress and the administration of propranolol and clonidine, we observed increased capillary fenestration and endothelial gaps. Similarly, propranolol increased the extravasation of Evans blue-labeled albumin in the skin tissue. We concluded that heat acclimation reinforces a mechanism by which the activation of adrenergic signal transduction pathways alters microvessel permeability during heat stress. Consequently the flux of plasma proteins and water into the interstitial space is accelerated, providing an interstitial source of water for sustained cutaneous evaporative cooling.
Sex differences in body weight gains following amygdaloid lesions in rats
Authors: King Bruce M. , Rollins Bethany L. , Stines Samuel G. , Cassis Sofia A. , McGuire Holland B. , Lagarde Michelle L.
Published: December 2017

Lesions of the most posterodorsal aspects of the amygdala resulted in equal weight gains (mean = 58 g) in male and female rats during a 22-day observation period. However, the absolute weight gains in the first 5 days after lesions were greater in females (+41.4 g) than in males (+18.8 g), as were the longer-term gains relative to their respective control groups. In a second study with female rats, it was found that amygdaloid lesions had little effect on the estrous cycle and that ovariectomy resulted in additional excessive weight gains in both rats with sham lesions and those with amygdaloid lesions. The weight gains produced by amygdaloid lesions and ovariectomy were additive. It is concluded that there is a sex difference in weight gains after amygdaloid lesions, but that the lesion-induced obesity is independent of estrogen levels. Similarities to lesions of the ventromedial hypothalamus are noted, and an amygdaloid-ventromedial hypothalamic pathway for the regulation of feeding behavior is proposed.
Nitric oxide modulates spontaneous swallowing behavior in near-term ovine fetus
Authors: El-Haddad Mostafa A. , Chao Conrad R. , Ma Sheng-Xing , Ross Michael G.
Published: December 2017

Human and ovine fetuses demonstrate an enhanced rate of swallowing, an activity critical for amniotic fluid regulation. Fetal swallowing may be modulated by both systemic and central factors. Nitric oxide (NO) is a central neuromodulator that has been localized to brain regions regulating thirst and swallowing. We sought to determine if NO contributes to the regulation of spontaneous ovine fetal swallowing. Six time-dated pregnant ewes with singleton fetuses (129 ± 1 day) were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram (ECoG) and esophageal electromyogram electrodes. After a 2-h control period, fetuses were given lateral ventricle injection of NO synthase inhibitor nitro-l-arginine methyl ester (l-NAME) and monitored for 2 h. NO precursor l-arginine was then injected into the lateral ventricle, and fetuses were monitored for a final 2 h. All fetuses received an additional control study of fetal swallowing before and after lateral ventricle injection of artificial cerebrospinal fluid (aCSF). Data were analyzed with repeated-measures ANOVA and paired t-test ( P < 0.05). Suppression of a central NO with central l-NAME significantly reduced mean (±SE) spontaneous fetal swallowing (1.2 ± 0.1–0.6 ± 0.1 swallows/min low-voltage ECoG; P < 0.01). Restoration of central NO by l-arginine significantly increased fetal swallowing to pre-l-NAME levels (1.2 ± 0.1 swallows/min low voltage). There were no changes in fetal swallowing during the control study of aCSF. Fetal ECoG activity and blood pressure did not change during the study or control aCSF injection. We conclude that NO is an important neuromodulator of fetal swallowing activity. Central NO synthase activity may contribute to the heightened level of spontaneous fetal swallowing and thus amniotic fluid regulation.
Coronary flow regulation in the fetal sheep
Authors: Thornburg Kent L. , Reller Mark D.
Published: December 2017

The two ventricles of the fetal sheep heart have anatomic and biochemical differences that account for their differing functional capabilities and blood flows. Coronary flows to both ventricles have been measured using radiolabeled microspheres [or left ventricular (LV) flow, by Doppler sensor on the circumflex coronary artery] during experiments of pressure loading and chronic and acute hypoxemia. Blood flow to the left ventricle with its lower wall tension is about two-thirds the flow per gram compared with the right ventricle (RV). Acute systolic pressure loading of the RV to its maximal work capability stimulates flow to double (from ∼250 to 500 ml ⋅ min−1 ⋅ 100 g−1), but to a level less than stimulated by adenosine (750 ml ⋅ min−1 ⋅ 100 g−1). At all RV work loads, LV flow remains at two-thirds RV flow. Resting myocardial flow levels in fetuses that have been chronically hypoxemic are similar to maximal adenosine-stimulated flows of normal fetal sheep. This flow augmentation is evidently due to vascular remodeling because a normal “flow reserve” of ∼500 ml ⋅ min−1 ⋅ 100 g−1 during adenosine administration remains. Acute hypoxemia stimulates myocardial flow to extraordinary levels (>1.5 l ⋅ min−1 ⋅ 100 g−1), levels larger than can be obtained with chemical dilation alone. LV flows do not exceed adenosine-stimulated flows when nitric oxide synthase is antagonized. We conclude 1) fetal RV coronary flow increases with RV work but to levels less than during adenosine stimulation; 2) the fetal heart is designed to accommodate extremely high flows in response to acute hypoxemia, partially through large production of nitric oxide; and 3) the fetal coronary tree is dramatically remodeled in response to chronic hypoxemia.
Effects of physiological or pathological pressure load in vivo on myocardial expression of ET-1 and receptors
Authors: Ueno Michihiko , Miyauchi Takashi , Sakai Satoshi , Kobayashi Tsutomu , Goto Katsutoshi , Yamaguchi Iwao
Published: December 2017

Endothelin (ET)-1 has potent positive inotropic and chronotropic activity in the heart and induces cardiac hypertrophy. The production of ET-1 in the heart is reported to be increased under some conditions. In normal circulation, the pressure load to the left ventricle (LV) is much greater than that to the right ventricle (RV). In this study, we investigated the gene expression of the myocardial ET-1 system (ET-1, ETAreceptor, and ETBreceptor) in the RV and LV of normal rats and also investigated these genes in hypertrophied RV due to pathological pulmonary hypertension (PH). Normal rats showed no differences between the RV and LV in the gene expression of either ET-1, ETAreceptor, or ETBreceptor in either the adult stage (11 wk old) or the neonatal stage (1 and 8 days old). On the other hand, the expression of both atrial natriuretic peptide (ANP) mRNA and B-type natriuretic peptide (BNP) mRNA was significantly greater in the LV than in the RV in adult rats. Gene expression of ET-1, ETAreceptor, and ETBreceptor in the RV was markedly higher in rats with monocrotaline-induced (pathological) PH than that in control rats. The expression of ANP mRNA and BNP mRNA in the RV was also markedly higher in the rats with PH. In conclusion, the data suggest that gene expression of the ET-1 system in the myocardium is not affected by physiological pressure load in either the adult stage or neonatal stage; however, it is enhanced by pathological pressure overload such as that in PH.
Lactate metabolism during exercise: analysis by an integrative systems model
Authors: Cabrera Marco E. , Saidel Gerald M. , Kalhan Satish C.
Published: December 2017

To provide a framework for quantitative analysis of metabolic and transport processes associated with ATP production during exercise, we adapted a recently developed model that links cellular metabolism and its control to whole body responses at rest. The enhanced model is based on dynamic mass balances for glycogen, glucose, pyruvate (PY), lactate (LA), O2, and CO2 and is solved numerically to simulate responses to acute (<20 min), moderate exercise (i.e., below the LA threshold, less than ∼60% maximal rate of O2 uptake). Simulations of responses to a step change in muscle ATP turnover predict substrate changes in muscle, splanchnic, and other tissues compartments, as well as changes in other metabolites (e.g., NADH, ADP) whose reactions are coupled to the main reactions. Even a significant (64%) decrease in muscle O2concentration ([Formula: see text]) did not affect muscle O2 consumption. Model simulations of moderate exercise show that 1) muscle oxygenation is sufficient ([Formula: see text] >2 mM) even during the transient state; 2) transient increases in concentration of muscle LA and arterial concentration of LA are associated with increases in glycolysis from increases in ADP/ATP and in LA production associated with a rise in NADH/NAD; 3) muscle ADP/ATP reaches a higher steady state that stimulates glycolysis, glycogenolysis, and oxidative phosphorylation to match the ATP demand; and 4) muscle NADH/NAD reaches a lower steady state that stimulates LA oxidation. It is suggested that the continuous stimulation of ATP synthesis processes during moderate exercise is mainly due to a higher ADP/ATP, not to a higher NADH/NAD. Critical measurements needed to quantify metabolic control mechanisms are identified.
The mudskipper,Periophthalmodon schlosseri, actively transports NH 4 + against a concentration gradient
Authors: Randall D. J. , Wilson J. M. , Peng K. W. , Kok T. W. K. , Kuah S. S. L. , Chew S. F. , Lam T. J. , Ip Y. K.
Published: December 2017

Periophthalmodon schlosseri can maintain ammonia excretion rates and low levels of ammonia in its tissues when exposed to 8 and 30 mM NH4Cl, but tissue ammonia levels rise when the fish is exposed to 100 mM NH4Cl in 50% seawater. Because the transepithelial potential is not high enough to maintain the[Formula: see text] concentration gradient between blood and water, ammonia excretion under such a condition would appear to be active. Branchial Na+-K+-ATPase activity is very high and can be activated by physiological levels of[Formula: see text] instead of K+. Ammonia excretion by the fish against a concentration gradient is inhibited by the addition of ouabain and amiloride to the external medium. It is concluded that Na+-K+-ATPase and an Na+/H+exchanger may be involved in the active excretion of ammonia across the gills. This unique ability of P. schlosseri to actively excrete ammonia is related to the special structure of its gills and allows the fish to continue to excrete ammonia while air exposed or in its burrow.
Effect of endogenous kinins, prostanoids, and NO on kinin B1and B2receptor expression in the rabbit
Authors: Marceau François , Larrivée Jean-François , Bouthillier Johanne , Bachvarova Magdalena , Houle Steeve , Bachvarov Dimcho R.
Published: December 2017

To determine whether kinin receptor expression is regulated by kinins, prostaglandins, and/or nitric oxide (NO), rabbits were treated with a B1receptor (B1R) antagonist, a B2receptor (B2R) antagonist, a prostacyclin mimetic, or inhibitors of NO synthase, cyclooxygenase, or angiotensin-converting enzyme. The mRNA concentrations for B1R and B2R (multiplex RT-PCR) were measured in several organs. The B2R mRNA expression was not significantly upregulated by any of the treatments; it was notably downregulated by angiotensin-converting enzyme or cyclooxygenase blockade or B2R antagonism in the heart and duodenum. A treatment with bacterial lipopolysaccharide (LPS), known to induce B1R expression, has also been applied and was the most consistent in upregulating the expression of B1R mRNA (kidney, duodenum, and striated muscle). The contractile responses mediated by kinin receptors in blood vessels isolated from the treated rabbits also indicated that LPS was the only B1R inducer (aorta). Icatibant, a nonequilibrium antagonist of the rabbit B2R, was the sole tested drug to alter the contractions mediated by the B2R in the jugular vein or the intensity of the immunohistochemical B2R staining in several organs (inhibition in both cases). B2R mRNA expression was downregulated in some organs by several of the applied treatments, but the data did not support generally applicable feedback for the regulation of B2R expression involving endogenous kinins, prostanoids, or NO. There was no indication of compensatory or reciprocal regulation of B1Rs, relative to B2Rs, inasmuch as B1R expression was restricted to LPS-treated animals.
Energetic dependence of NPY-induced LH secretion in a teleost fish (Dicentrarchus labrax)
Authors: Cerdá-Reverter José Miguel , Sorbera Lisa Ann , Carrillo Manuel , Zanuy Silvia
Published: December 2017

The purpose of this work was to examine the role of energetic status in neuropeptide Y (NPY)-induced luteinizing hormone (LH) secretion and glucose metabolism in fish. Fasted juvenile sea bass ( Dicentrarchus labrax) were injected intraperitoneally with pig (p) NPY or pNPY + glucose, whereas fed animals were injected with pNPY alone and plasma glucose, insulin, and LH levels were examined. pNPY alone or in combination with glucose was found to induce a dose-dependent increase in LH secretion in fasted animals. Similar LH responses to pNPY were observed in vitro in dispersed pituitary cells isolated from fed and fasted animals incubated in L-15 and restricted media. Injection of pNPY + glucose in fasted animals resulted in depletion of glucose. Insulin plasma levels decreased in fasted animals coinjected with pNPY + glucose but remained stable when NPY was administrated alone to fed and fasted animals. Results suggest that 1) NPY-induced LH secretion in fish is dependent on energetic status and 2) NPY is capable of modifying glucose metabolism.
Influence of hemodilution on the renal blood flow autoregulation during acute expansion in rats
Authors: Franchini Kleber G.
Published: December 2017

Autoregulation of renal blood flow (RBF) was studied in rats that underwent equivalent blood volume expansion with saline (Sal; 5% body wt), 7% BSA solution (1.4% body wt), and reconstituted whole blood from donor rats (WBL; 1.4% body wt). Renal perfusion pressure (RPP) and renal neural reflexes were prevented by clamping RPP and sectioning the vagus, baro/chemoreceptor, and renal nerves. Sal and BSA expansion increased RBF by ∼60%, whereas no effect was observed with WBL. RBF autoregulation was markedly attenuated after expansion with cell-free solutions, but no change occurred in WBL-expanded rats. Correction of the fall in hematocrit in Sal- and BSA-expanded rats restored RBF and its autoregulation to control levels. Expansion with Sal or BSA after inhibition of renal vascular tone with intrarenal infusion of papaverine still increased RBF and further changed the RBF-RPP relationship. These findings suggest that the hemodilution plays a central role in the reduction of renal vascular resistance and in the attenuation of the autoregulatory efficiency of renal circulation that accompany expansion with cell-free solutions.
Muscle fiber type specificity in insulin signal transduction
Authors: Song Xiao Mei , Ryder Jeffrey W. , Kawano Yuichi , Chibalin Alexander V. , Krook Anna , Zierath Juleen R.
Published: December 2017

We determined the muscle fiber type-specific response of intracellular signaling proteins to insulin. Epitrochlearis (Epi; 15% type I, 20% type IIa, and 65% type IIb), soleus (84, 16, and 0%), and extensor digitorum longus (EDL; 3, 57, and 40%) muscles from Wistar rats were incubated without or with 120 nM insulin (3–40 min). Peak insulin receptor (IR) tyrosine phosphorylation was reached after 6 (soleus) and 20 (Epi and EDL) min, with sustained activity throughout insulin exposure (40 min). Insulin increased insulin receptor substrate (IRS)-1 and IRS-2 tyrosine phosphorylation and phosphotyrosine-associated phosphatidylinositol (PI)-3-kinase activity to a maximal level after 3–10 min, with subsequent downregulation. Akt kinase phosphorylation peaked at 20 min, with sustained activity throughout insulin exposure. Importantly, the greatest insulin response for all signaling intermediates was observed in soleus, whereas the insulin response between EDL and Epi was similar. Protein expression of the p85α-subunit of PI 3-kinase and Akt kinase, but not IR, IRS-1, or IRS-2, was greater in oxidative versus glycolytic muscle. In conclusion, increased function and/or expression of key proteins in the insulin-signaling cascade contribute to fiber type-specific differences in insulin action in skeletal muscle.
Inhibition of food intake in response to intestinal lipid is mediated by cholecystokinin in humans
Authors: Matzinger Daniel , Gutzwiller Jean-Pierre , Drewe Juergen , Orban Amar , Engel Reto , D'Amato Massimo , Rovati Lucio , Beglinger Christoph
Published: December 2017

Intraduodenal fat inhibits gastric emptying and exerts early satiation in animals and humans, but it is not clear whether the effects are mediated by cholecystokinin (CCK) in humans. Here, we tested whether CCK-A receptors mediate the inhibition of fat on food intake. Two sequential, double-blind, crossover studies were performed in 24 male subjects. First, subjects received either intraduodenal fat or saline together with a preload of either water or banana shake. Second, 12 subjects received either intraduodenal fat or saline perfusion plus a concomitant infusion of saline or loxiglumide, a specific CCK-A receptor antagonist, together with a preload of banana shake. In both studies, subjects were free to eat and drink as much as they wished. Fat induced a reduction in calorie intake ( P < 0.05) compared with controls. Furthermore, a decrease in hunger feelings was observed. Infusion of loxiglumide abolished the effects of fat. Duodenal fat interacts with an appetizer to modulate energy intake in humans. This effect is mediated by CCK-A receptors.
Sympathetic and cardiovascular actions of orexins in conscious rats
Authors: Shirasaka Tetsuro , Nakazato Masamitsu , Matsukura Shigeru , Takasaki Mayumi , Kannan Hiroshi
Published: December 2017

The novel hypothalamic peptides orexin-A and orexin-B are known to induce feeding behavior when administered intracerebroventricularly, but little is known about other physiological functions. The renal sympathetic nerves play important roles in the homeostasis of body fluids and the circulatory system. We examined the effects of intracerebroventricularly administered orexins on mean arterial pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and plasma catecholamine in conscious rats. Orexin-A (0.3, 3.0 nmol) provoked an increase in MAP (94.3 ± 0.7 to 101.9 ± 0.7 mmHg and 93.1 ± 1.1 to 108.3 ± 0.8 mmHg, respectively) and RSNA (28.0 ± 7.0 and 57.9 ± 12.3%, respectively). Similarly, orexin-B (0.3, 3.0 nmol) increased MAP (93.9 ± 0.9 to 97.9 ± 0.9 mmHg and 94.5 ± 1.1 to 105.3 ± 1.7 mmHg, respectively). Orexin-A and -B at 3.0 nmol also increased HR. In other conscious rats, a high dose of orexin-A and -B increased plasma norepinephrine. Plasma epinephrine only increased with a high dose of orexin-A. These results indicate that central orexins regulate sympathetic nerve activity and affect cardiovascular functions.
Pregnancy alters cardiac receptor afferent discharge in rats
Authors: Hines Tina , Hodgson Tracy M.
Published: December 2017

Reflex effects of cardiac receptor (CR) stimulation are attenuated in pregnant rats. We tested whether CR afferent discharge is reduced during pregnancy by measuring single fiber activity in response to increases in right atrial pressure (RAP) in anesthetized pregnant and virgin rats with sinoaortic denervation. Single fiber activity was isolated from fine filaments of the right cervical vagus nerve. Changes in CR discharge, RAP, and arterial pressure were recorded in response to atrial saline injections (25–300 μl). Resting RAP was similar between groups, and spontaneous CR discharge was similar in pregnant rats (1.95 ± 0.21 Hz) and in low-frequency (LF) receptors in virgin rats (1.30 ± 0.2 Hz). In virgin, but not pregnant rats, a subset (24%) of CR had higher-frequency (HF) spontaneous discharge (9.91 ± 1.19 Hz). During stimulation, the level of RAP above which CR firing increased was significantly higher in pregnant rats, but CR activity was clustered into an LF discharge range. Thus gestation appears to reduce the activity of CR afferents, possibly by increasing stimulus threshold or by selective inactivation of a subset of HF discharging receptors.
Effects of feeding on metabolism, gas transport, and acid-base balance in the bullfrogRana catesbeiana
Authors: Busk Morten , Jensen Frank B. , Wang Tobias
Published: December 2017

Massive feeding in ectothermic vertebrates causes changes in metabolism and acid-base and respiratory parameters. Most investigations have focused on only one aspect of these complex changes, and different species have been used, making comparison among studies difficult. The purpose of the present study was, therefore, to provide an integrative study of the multiple physiological changes taking place after feeding. Bullfrogs ( Rana catesbeiana) partly submerged in water were fed meals (mice or rats) amounting to ∼[Formula: see text] of their body weight. Oxygen consumption increased and peaked at a value three times the predigestive level 72–96 h after feeding. Arterial[Formula: see text] decreased slightly during digestion, whereas hemoglobin-bound oxygen saturation was unaffected. Yet, arterial blood oxygen content was pronouncedly elevated because of a 60% increase in hematocrit, which appeared mediated via release of red blood cells from the spleen. Gastric acid secretion was associated with a 60% increase in plasma [Formula: see text]concentration[Formula: see text]]) 48 h after feeding. Arterial pH only increased from 7.86 to 7.94, because the metabolic alkalosis was countered by an increase in[Formula: see text] from 10.8 to 13.7 mmHg. Feeding also induced a small intracellular alkalosis in the sartorius muscle. Arterial pH and [Formula: see text] returned to control values 96–120 h after feeding. There was no sign of anaerobic energy production during digestion as plasma and tissue lactate levels remained low and intracellular ATP concentration stayed high. However, phosphocreatine was reduced in the sartorius muscle and ventricle 48 h after feeding.
Expression of CD44 in kidney after acute ischemic injury in rats
Authors: Lewington Andrew J. P. , Padanilam Babu J. , Martin Daniel R. , Hammerman Marc R.
Published: December 2017

De novo CD44 and ligand expression at wound margins accompanies cellular proliferation and migration that effect repair of injured mucosal and vascular endothelial tissues. To determine whether CD44 could play a role in recovery from acute ischemic renal injury, we characterized its renal expression and those of two of its ligands, hyaluronic acid and osteopontin. Although no expression is detectable in nonischemic kidneys, several mRNAs for CD44 are present within 1 day after injury. CD44 mRNA is expressed in proximal tubules undergoing repair. CD44 peptide is present in basal and lateral cell membranes. Hyaluronic acid is normally expressed in the interstitium of the renal papilla only. By 1 day postischemia, hyaluronic acid can be detected, in addition, in the interstitium surrounding regenerating tubules. Osteopontin, not normally expressed in the renal proximal tubule, is expressed in regenerating tubules by 3 days after induction of acute ischemic injury. Immunoreactive osteopontin peptide continues to be localized in those tubules still undergoing repair for as long as 7 days after the injury. Our data are consistent with a role for CD44-ligand interactions in the regenerating proximal tubule participating in the process of recovery after ischemic injury.
Concurrent reductions in blood pressure and metabolic rate during fasting in the unrestrained SHR
Authors: Williams T. D. , Chambers J. B. , May O. L. , Henderson R. P. , Rashotte M. E. , Overton J. M.
Published: December 2017

Fasting produces multiple cardiovascular, metabolic, and behavioral responses. To examine the interrelationship between these responses, male spontaneously hypertensive rats (SHR; n = 8) implanted with cardiovascular telemetry devices were housed in metabolic chambers at 23°C for 22-h daily measurements of physiological variables. The experimental apparatus was designed so that ingestive behavior was detected by photobeams and locomotion was detected by a load sensor. Cardiovascular and metabolic status were determined as both a function of the circadian cycle (12-h dark and 10-h light), as well as during periods of inactivity (no ingestion and minimal locomotion) within the dark and light phases. Data were obtained during baseline, 48-h of caloric deprivation, and 6 days of refeeding. Fasting produced significant reductions in mean arterial pressure (dark: −9.2 ± 1.3 from 143.7 ± 3.7 mmHg; light: −8.6 ± 1.8 from 140.1 ± 3.7 mmHg), heart rate (dark: −43.4 ± 5.2 from 330.0 ± 5.2 beats/min; light: −27.4 ± 5.2 from 294.0 ± 5.2 beats/min), and oxygen consumption (dark: −5.0 ± 0.6 from 20.6 ± 0.3 ml ⋅ min−1⋅ kg0.75; light: −2.7 ± 0.2 from 14.9 ± 0.2 ml ⋅ min−1⋅ kg0.75). Analysis of inactive periods during both light and dark phases revealed that these reductions were not dependent on behavioral effects. We conclude that fasting produces concurrent and interrelated reductions in cardiovascular and metabolic function in the SHR. The merging of cardiovascular telemetry, indirect calorimetry, and behavioral monitoring provides a powerful approach for investigation of the integrative physiological responses to energetic challenges.
Fluid extravasation from spleen reduces blood volume in endotoxemia
Authors: Andrew Peter , Deng Yiming , Kaufman Susan
Published: December 2017

We recently demonstrated that fluid is filtered out of the splenic circulation and into the lymphatic system. The current experiments were designed to investigate the importance of this route of fluid extravasation in endotoxemia. Lipopolysaccharide (LPS) was infused into conscious intact and splenectomized rats (150 μg ⋅ kg−1⋅ h−1iv for 18 h). In the intact rats, mean arterial pressure (MAP) fell from 101 ± 2.4 to 88 ± 3.9 mmHg ( n = 7) and then stabilized at about 90 mmHg. Hematocrit rose from 41 ± 0.9 to 45 ± 0.4% at 40 min, at which time plasma volume had fallen from 4.7 ± 0.12 to 4.0 ± 0.05 ml/100 g body wt. In the splenectomized rats MAP did not fall and hematocrit did not rise. There also was no change in plasma volume, i.e., splenectomy prevented the hypotension and hemoconcentration customarily induced by LPS. In a second series of experiments, splenic arterial and venous blood flows were simultaneously measured in anesthetized rats infused with LPS (150 μg ⋅ kg−1⋅ h−1). LPS increased splenic fluid efflux. We conclude that during endotoxemia the initial fall in circulating blood volume may be attributed to fluid extravasation from the splenic vasculature.
Nitric oxide release and contractile properties of skeletal muscles from mice deficient in type III NOS
Authors: Hirschfield Wulf , Moody Melanie R. , O'Brien William E. , Gregg Anthony R. , Bryan Robert M. , Reid Michael B.
Published: December 2017

Skeletal muscle constitutively expresses both the type I (neuronal) and type III (endothelial) isoforms of nitric oxide synthase (NOS). We tested the functional importance of type III NOS using skeletal muscles with similar levels of type III NOS expression (diaphragm and soleus) from wild-type, heterozygous, and type III NOS-deficient littermate mice. Muscles were incubated at 37°C in Krebs-Ringer solution. NO accumulation in the medium was measured by chemiluminescence; force-frequency and fatigue characteristics were measured using direct electrical stimulation. Diaphragm and soleus released NO at similar rates during passive incubation; these rates increased during active contraction. NO release by type III NOS-deficient muscle was not different from that of wild-type muscle under any condition tested. Force-frequency and fatigue characteristics also were unaffected by genotype. Because type III NOS deficiency did not alter function, we conclude that NO effects previously observed in wild-type muscle are likely to be mediated by type I NOS.
Pregnancy-associated reduction in vascular protein kinase C activity rebounds during inhibition of NO synthesis
Authors: Kanashiro Celia A. , Cockrell Kathy L. , Alexander Barbara T. , Granger Joey P. , Khalil Raouf A.
Published: December 2017

Vascular reactivity has been shown to be reduced during pregnancy and to be enhanced during chronic inhibition of nitric oxide (NO) synthesis in pregnant rats; however, the cellular mechanisms involved are unclear. The purpose of this study was to investigate whether the pregnancy-induced changes in vascular reactivity are associated with changes in the amount and/or activity of vascular protein kinase C (PKC). Active stress as well as the amount and activity of PKC was measured in deendothelialized thoracic aortic strips from virgin and pregnant rats untreated or treated with the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME). In virgin rats, the PKC activator phorbol 12,13-dibutyrate (PDBu, 10−6M) and the α-adrenergic agonist phenylephrine (Phe, 10−5M) caused significant increases in active stress and PKC activity that were inhibited by the PKC inhibitors staurosporine and calphostin C. Western blot analysis in aortic strips of virgin rats showed significant amount of the α-PKC isoform. Both PDBu and Phe caused significant translocation of α-PKC from the cytosolic to the particulate fraction. Compared with virgin rats, the PDBu- and Phe-stimulated active stress and PKC activity as well as the amount and the PDBu- and Phe-induced translocation of α-PKC were significantly reduced in late pregnant rats but significantly enhanced in pregnant rats treated withl-NAME. The PDBu- and Phe-induced changes in active stress and the amount, distribution, and activity of α-PKC in virgin rats treated with l-NAME were not significantly different from that in virgin rats, whereas the changes in pregnant rats treated withl-NAME + the NO synthase substrate l-arginine were not significantly different from that in pregnant rats. These results provide evidence that a PKC-mediated contractile pathway in vascular smooth muscle is reduced during pregnancy and significantly enhanced during chronic inhibition of NO synthesis. The results suggest that one possible mechanism of the pregnancy-associated changes in vascular reactivity may involve changes in the amount and activity of the α-PKC isoform.
Effects of intraduodenal glucose and fructose on antropyloric motility and appetite in healthy humans
Authors: Rayner C. K. , Park H. S. , Wishart J. M. , Kong M.-F. , Doran S. M. , Horowitz M.
Published: December 2017

Oral fructose empties from the stomach more rapidly and may suppress food intake more than oral glucose. The purpose of the study was to evaluate the effects of intraduodenal infusions of fructose and glucose on antropyloric motility and appetite. Ten healthy volunteers were given intraduodenal infusions of 25% fructose, 25% glucose, or 0.9% saline (2 ml/min for 90 min). Antropyloric pressures, blood glucose, and plasma insulin, gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) were measured concurrently; a buffet meal was offered at the end of the infusion. Intraduodenal fructose and glucose suppressed antral waves ( P < 0.0005 for both), stimulated isolated pyloric pressure waves ( P < 0.05 for both), and increased basal pyloric pressure ( P = 0.10 and P < 0.05, respectively) compared with saline, without any significant difference between them. Intraduodenal glucose increased blood glucose ( P < 0.0005), as well as plasma insulin ( P < 0.0005) and GIP ( P < 0.005) more than intraduodenal fructose, whereas there was no difference in the GLP-1 response. Intraduodenal fructose suppressed food intake compared with saline ( P < 0.05) and glucose ( P = 0.07). We conclude that, when infused intraduodenally at 2 kcal/min for 90 min 1) fructose and glucose have comparable effects on antropyloric pressures, 2) fructose tends to suppress food intake more than glucose, despite similar GLP-1 and less GIP release, and 3) GIP, rather than GLP-1, probably accounts for the greater insulin response to glucose than fructose.
Sodium intake is increased by social stress and the Y chromosome and reduced by clonidine
Authors: Ely Daniel , Herman Michael , Ely Lawrence , Barrett Linda , Milsted Amy
Published: December 2017

The objectives were to determine 1) if female rats have higher Na intake than males and if social stress increases Na intake, 2) if the sympathetic nervous system (SNS) mediates the stress effects and the gender effect, and 3) if the Y chromosome (Yc) from a hypertensive father increases Na intake. Four rat strains ( n = 10/group) of both sexes were used: 1) Wistar Kyoto normotensive (WKY), 2) an F16 backcross with a Yc from a hypertensive father (SHR/y), 3) spontaneously hypertensive rat (SHR), and 4) an F16 backcross with a Yc from a normotensive father (SHR/a). Females showed greater baseline Na intake than males (hypertensive strains), intruder stress increased Na intake, and clonidine decreased Na intake, but not in WKY or SHR females. SHR/y males had higher baseline Na intake compared with WKY males. In conclusion, the higher Na intake in females during baseline and stress was partially mediated through the SNS in hypertensive strains and the SHR Yc was partially responsible for the increased Na intake in SHR/y and SHR males compared with WKY.