bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary salt intake alters cardiovascular responses evoked from the rostral ventrolateral medulla
Authors: Ito Satoru , Gordon Frank J. , Sved Alan F.
Published: December 2017

The present experiments examined whether in rats consuming diets with either high NaCl content (8%) or low Na+content (0.01%) for 2 wk excitatory inputs to the rostral ventrolateral medulla (RVLM) would be altered. In chloralose-anesthetized rats, injection of glutamate into the RVLM elicited a pressor response that, compared with rats fed a control diet, was 50% larger in rats fed a diet containing 8% NaCl and was 25% smaller in rats fed a diet containing 0.01% Na+. Pressor responses produced by electrical stimulation of sciatic nerve afferents, as well as by microinjections into the RVLM ofl-dihydroxyphenylalanine or carbachol, were all potentiated by high dietary salt intake and reduced by low dietary salt intake. Dietary salt intake had no effect on pressor responses produced by intravenous injection of phenylephrine, indicating that salt-related alterations in cardiovascular responses produced by central activation could not be accounted for by changes in peripheral vascular reactivity. The decrease in arterial pressure produced by injection of glutamate into the nucleus of the solitary tract was also potentiated by the high salt diet, suggesting that the sensitivity of central baroreceptor reflex pathways may be altered by dietary NaCl. These results indicate that the amount of NaCl consumed in the diet can change the sensitivity of RVLM sympathoexcitatory neurons, and this change in sensitivity is not restricted to any particular class of cell surface receptors.
Cardiac- and noncardiac-related coherence between sympathetic drives to muscles of different human limbs
Authors: Kocsis Bernat , Karlsson Tomas , Wallin B. Gunnar
Published: December 2017

Partial coherence analysis was used to evaluate the extent to which coherence between resting muscle sympathetic activity (MSA) in different pairs of limbs in humans is explained by the common baroreceptor input and by other noncardiac-related factors. Multiunit MSA in two or three nerves, arterial blood pressure, and electrocardiogram were recorded simultaneously. Correlated MSA consisted of a sharp periodic component at the heart rate and a wideband component of relatively low power distributed between 0 and 2–2.5 Hz. Quantitative analysis revealed stronger coupling between MSAs in close limbs than in distant limbs (peak coherence leg-leg, 0.94 ± 0.03; arm-leg, 0.76 ± 0.11). Furthermore, the wideband component, unaffected by partialization with circulatory signals, was significantly stronger between leg-leg (0.67 ± 0.10) than between arm-leg pairs (0.29 ± 0.10), i.e., noncardiac-related components explained 71% of leg-leg and 38% of arm-leg coherences at the frequency of the heart. Our results indicate that nonuniform relationship exists between resting sympathetic outflow to muscles in close and distant extremities which is, however, partially masked by the effect of the common rhythmic baroreceptor input.
Ontogeny of estrogen sulfatase activity in ovine fetal hypothalamus, hippocampus, and brain stem
Authors: Purinton Scott C. , Newman Howard , Castro Maria I. , Wood Charles E.
Published: December 2017

Ovine parturition is initiated by increases in fetal hypothalamus-pituitary-adrenal (HPA) axis activity, which in turn increase placental estrogen biosynthesis and ultimately increase uterine contractility. In addition to the action in the uterus, estrogens augment fetal ACTH secretion. In late gestation, estrone sulfate is more abundant in fetal plasma than is unconjugated estrone. We studied hypothalamus, hippocampus, and brain stem tissue from fetal, neonatal, and adult sheep to test the hypothesis that the ovine brain contains estrogen sulfatase activity. We found that the activity in the hippocampus was significantly increased in late-gestation fetuses compared with both younger and older animals. No significant change in either hypothalamus or brain stem was revealed; however, the activity in all brain areas was high. Immunohistochemistry revealed the presence of estrogen sulfatase in the paraventricular nucleus of the hypothalamus, the nucleus of the solitary tract, and the rostral ventrolateral medulla. We conclude that ovine fetal hypothalamus, hippocampus, and brain stem contain estrogen sulfatase activity and that the activity in the hippocampus is developmentally regulated.
Basolateral regulation of pHiin isolated snake renal proximal tubules in presence and absence of bicarbonate
Authors: Dantzler William H. , Serrano Oscar K. , Abbott Diane E. , Kim Yung Kyu , Brokl Olga H.
Published: December 2017

Intracellular pH (pHi) and its basolateral regulation were studied in isolated proximal-proximal and distal-proximal segments of garter snake ( Thamnophis spp.) renal tubules with oil-filled lumens in HEPES-buffered and in HEPES-[Formula: see text]-buffered media (pH 7.4 at 25°C). pHi was measured with the pH-sensitive fluorescent dye 2′,7′-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF) under resting conditions and in response to NH4Cl pulse. Resting pHi (∼7.1–7.2) and its response to and rate of recovery (dpHi/d t) from an NH4Cl pulse were not affected by the presence or absence of[Formula: see text] in either segment. Rate of recovery was depressed by Na+removal in distal-proximal segments only and only in HEPES buffer. It was not affected by removal of Cl− or of both Na+ and Cl− or by reduction in membrane potential through addition of Ba2+ (5 mM) or high K+ (75 mM) in either segment in either HEPES or HEPES-[Formula: see text] buffer. The Na+/H+exchange inhibitor ethylisopropylamiloride (EIPA) (100 μM) and the anion exchange inhibitor DIDS (100 μM) reduced dpHi/d tin the distal-proximal segments only and only in HEPES-[Formula: see text] buffer. The H+-ATPase inhibitor bafilomycin (1 μM), H+-K+-ATPase and K+/[Formula: see text]exchange inhibitor Schering 28080 (10–100 μM), organic cation efflux inhibitor tetrapentylammonium (25 μM–20 mM), and K+ channel blocker tetraethylammonium (20 mM) had no effect on dpHi/d tin either segment. These data do not clearly support basolateral regulation of pHi in snake proximal renal tubules by commonly recognized Na+-dependent or Na+-independent acid or base transporters.
Comparative analysis of NMR and NIRS measurements of intracellular P O 2 in human skeletal muscle
Authors: Tran Tuan-Khanh , Sailasuta Napapon , Kreutzer Ulrike , Hurd Ralph , Chung Youngran , Mole Paul , Kuno Shinya , Jue Thomas
Published: December 2017

1H NMR has detected both the deoxygenated proximal histidyl NδH signals of myoglobin (deoxyMb) and deoxygenated Hb (deoxyHb) from human gastrocnemius muscle. Exercising the muscle or pressure cuffing the leg to reduce blood flow elicits the appearance of the deoxyMb signal, which increases in intensity as cellular[Formula: see text] decreases. The deoxyMb signal is detected with a 45-s time resolution and reaches a steady-state level within 5 min of pressure cuffing. Its desaturation kinetics match those observed in the near-infrared spectroscopy (NIRS) experiments, implying that the NIRS signals are actually monitoring Mb desaturation. That interpretation is consistent with the signal intensity and desaturation of the deoxyHb proximal histidyl NδH signal from the β-subunit at 73 parts per million. The experimental results establish the feasibility and methodology to observe the deoxyMb and Hb signals in skeletal muscle, help clarify the origin of the NIRS signal, and set a stage for continuing study of O2regulation in skeletal muscle.
Energy expenditure and balance during spaceflight on the space shuttle
Authors: Stein T. P. , Leskiw M. J. , Schluter M. D. , Hoyt R. W. , Lane H. W. , Gretebeck R. E. , LeBlanc A. D.
Published: December 2017

The objectives of this study were as follows: 1) to measure human energy expenditure (EE) during spaceflight on a shuttle mission by using the doubly labeled water (DLW) method; 2) to determine whether the astronauts were in negative energy balance during spaceflight; 3) to use the comparison of change in body fat as measured by the intake DLW EE,18O dilution, and dual energy X-ray absorptiometry (DEXA) to validate the DLW method for spaceflight; and 4) to compare EE during spaceflight against that found with bed rest. Two experiments were conducted: a flight experiment ( n = 4) on the 16-day 1996 life and microgravity sciences shuttle mission and a 6° head-down tilt bed rest study with controlled dietary intake ( n = 8). The bed rest study was designed to simulate the flight experiment and included exercise. Two EE determinations were done before flight (bed rest), during flight (bed rest), and after flight (recovery). Energy intake and N balance were monitored for the entire period. Results were that body weight, water, fat, and energy balance were unchanged with bed rest. For the flight experiment, decreases in weight (2.6 ± 0.4 kg, P < 0.05) and N retention (−2.37 ± 0.45 g N/day, P < 0.05) were found. Dietary intake for the four astronauts was reduced in flight (3,025 ± 180 vs. 1,943 ± 179 kcal/day, P < 0.05). EE in flight was 3,320 ± 155 kcal/day, resulting in a negative energy balance of 1,355 ± 80 kcal/day (−15.7 ± 1.0 kcal ⋅ kg−1 ⋅ day−1, P < 0.05). This corresponded to a loss of 2.1 ± 0.4 kg body fat, which was within experimental error of the fat loss determined by18O dilution (−1.4 ± 0.5 kg) and DEXA (−2.4 ± 0.4 kg). All three methods showed no change in body fat with bed rest. In conclusion, 1) the DLW method for measuring EE during spaceflight is valid, 2) the astronauts were in severe negative energy balance and oxidized body fat, and 3) in-flight energy (E) requirements can be predicted from the equation: E = 1.40 × resting metabolic rate + exercise.
Nuclear factor-κB-like activity increases in murine cerebral cortex after sleep deprivation
Authors: Chen Zutang , Gardi Janos , Kushikata Tetsuya , Fang Jidong , Krueger James M.
Published: December 2017

Several well-defined sleep regulatory substances, e.g., interleukin-1β, activate the heterodimeric transcription factor nuclear factor-κB (NF-κB). Several substances that inhibit sleep, e.g., interleukin-4, inhibit NF-κB activation. NF-κB activation promotes production of several additional substances thought to be involved in sleep regulation, e.g., nitric oxide. We investigated, therefore, whether there are diurnal rhythms of NF-κB activation in brain and changes in the activation after sleep deprivation. Mice were kept on a 12:12-h light-dark cycle. In one experiment, groups of mice were killed every 3 h across the 24-h cycle. In another experiment, mice were killed at 1500 after 6 h of sleep deprivation, and a group of control mice were killed at the same time. Nuclear proteins were extracted from each brain tissue sample, and NF-κB-like activity was determined with an electrophoretic mobility shift assay. In cerebral cortex, but not other areas of brain, there was a diurnal rhythm in NF-κB-like activation; highest levels were found during the light period. NF-κB-like activation was higher in cerebral cortex after sleep deprivation compared with values obtained from control mice. The results are consistent with the hypothesis that sleep regulation involves multiple gene events, some of which include enhanced production of sleep regulatory substances, the actions of which involve NF-κB activation.
Threshold for efferent bladder nerve firing in the rat
Authors: van Asselt Els , le Feber Joost , van Mastrigt Ron
Published: December 2017

In this study, the mechanism involved in the initiation of voiding was investigated. Bladder pressure and bladder and urethral nerve activity were recorded in the anesthetized rat. Bladder nerve activity was resolved into afferent and efferent activity by means of a theoretical model. The beginning of an active bladder contraction was defined as the onset of bladder efferent firing at a certain time ( t 0). From t 0 onward, bladder efferent activity increased linearly during δ t seconds (rise time) to a maximum. The pressure at t 0 was 1.0 ± 0.4 kPa, the afferent nerve activity at t 0 was 2.0 ± 0.6 μV (53 ± 15% of maximum total nerve activity), and δ t was 11 ± 13 s. Between contractions the afferent activity at t 0 was never exceeded. Urethral afferent nerve activity started at bladder pressures of 2.1 ± 1.1 kPa. Therefore, we concluded that urethral afferent nerve activity does not play a role in the initiation of bladder contractions; voiding contractions presumably are initiated by bladder afferent nerve activity exceeding a certain threshold.
Chemical composition of saccular endolymph and otolith in fish inner ear: lack of spatial uniformity
Authors: Payan Patrick , Edeyer Anaick , de Pontual Hélène , Borelli Gil , Boeuf Gilles , Mayer-Gostan Nicole
Published: December 2017

Fish otoliths provide a record of age, growth, and environmental influences. In both trout and turbot, spatial chemical investigation of the endolymph surrounding the otolith (sagitta) showed a lack of uniformity. Proteins, [Formula: see text], and Mg2+were significantly more concentrated in the proximal (facing the macula) than distal zone, whereas the opposite was observed for K+and total CO2(totCO2). Na+concentration ([Na+]) was 20% higher in the proximal zone in trout but not in turbot. Total Ca and Cl−contents were uniformly distributed in both species. We propose that the endolymphatic gradients of protein and totCO2concentration within the endolymph are involved in the otolithic biocalcification process. Microchemical analyses of otolith sections by wavelength dispersive spectrometry showed a lack of spatial uniformity in the K/Ca and Na/Ca ratios, whereas the Sr/Ca ratio was uniform. There is a clear relationship between endolymph and otolith [K+], but the interpretation of the results for [Na+] needs further investigation. Thus the lack of uniformity in the otolith composition must be taken into account when investigating otolith microchemistry.
Transcriptional and posttranscriptional regulation of β2-adrenergic receptor gene in rat liver during sepsis
Authors: Yang Jun , Dong Lin-Wang , Tang Chaoshu , Liu Maw-Shung
Published: December 2017

Changes in β2-adrenergic receptor (β2-AR) gene expression in the rat liver during different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats exhibit two metabolically distinct phases: an initial hyperglycemic (9 h after CLP; early sepsis) followed by a hypoglycemic phase (18 h after CLP; late sepsis). The [3H]dihydroalprenolol binding studies show that the density of β2-AR was decreased by 12 and 35% during the early and late phases of sepsis, respectively. Western blot analyses depict that the β2-AR protein level was reduced by 37 and 72% during early and late sepsis, respectively. The reverse transcription polymerase chain reaction and Southern blot analyses reveal that the steady-state level of β2-AR mRNA was decreased by 37% during early phase and 77% during late phase of sepsis. Nuclear run-off assays show that the rate of transcription of β2-AR mRNA was reduced by 36% during early sepsis and 64% during late sepsis. The stability assays indicate that the half-life of β2-AR mRNA was shortened by 21 and 50% during the early and late phases of sepsis, respectively, indicating that the rate of degradation of β2-AR mRNA was progressively enhanced during sepsis. These findings demonstrate that the β2-AR gene was underexpressed in the liver during the progression of sepsis, and, furthermore, the underexpression of the β2-AR gene was the result of a reduction in the rate of transcription coupled with an enhancement in the rate of degradation of β2-AR gene transcripts. Thus our findings that the transcriptional and posttranscriptional regulation of β2-AR gene associated with decreases in β2-AR number and its protein expression may provide a molecular mechanistic explanation for the development of hypoglycemia during the late stage of sepsis.
Differential regulation of functional responses by β-adrenergic receptor subtypes in brown adipocytes
Authors: Chaudhry Archana , Granneman James G.
Published: December 2017

Brown adipose tissue contains both β1- and β3-adrenergic receptors (β-ARs), and whereas both receptor subtypes can activate adenylyl cyclase, recent studies suggest that these subtypes have different pharmacological properties and may serve different signaling functions. In this study, primary brown adipocyte cultures were used to determine the role of β-AR subtypes in mediating lipolysis and uncoupling protein-1 (UCP1) gene expression, elicited by the physiological neurohormone norepinephrine (NE). NE increased both lipolysis and UCP1 mRNA levels in brown adipocyte cultures; the β1-receptor-selective antagonist CGP-20712A strongly antagonized the increase in UCP1 gene expression but had little effect on lipolysis. The β3-receptor-selective agonist CL-316243 (CL) also increased lipolysis and UCP1 mRNA levels, yet CL was more potent in stimulating lipolysis than UCP1 gene expression. NE also increased the phosphorylation of cAMP response element-binding protein (CREB) and perilipin (PL), both of which are protein kinase A substrates that are differentially targeted to the nucleus and lipid droplets, respectively. β1-receptor blockade inhibited NE-stimulated phosphorylation of CREB but not PL. The results suggest that β-AR subtypes regulate different physiological responses stimulated by NE in brown adipocyte cultures in part by differentially transducing signals to subcellular compartments.
Pulmonary artery endothelium-dependent vasodilation is impaired in a chicken model of pulmonary hypertension
Authors: Martinez-Lemus Luis A. , Hester R. Kelly , Becker Elizabeth J. , Jeffrey Joan S. , Odom Ted W.
Published: December 2017

Among chicken strains, broilers are prone to pulmonary hypertension, whereas Leghorns are not. Relaxations to endothelium-dependent (ACh, A23187) and endothelium-independent [sodium nitroprusside (SNP), papaverine (PPV)] vasodilators were compared in preconstricted pulmonary artery (PA) rings from these chicken strains. ACh (10−7, 10−6, and 10−5 M)- and A23187 (10−6 and 10−5.5 M)-induced relaxations were smaller ( P < 0.05) in broilers than Leghorns. N G-nitro-l-arginine methyl ester (10−3.5 M) caused similar reductions in ACh-induced relaxations in both strains.l-Arginine (10−4 M) enhanced ACh-induced relaxations more in broilers than Leghorns. Relaxations to 10−10–10−6M SNP did not differ between strains, but were greater ( P < 0.05) in broilers than Leghorns at higher concentrations (10−5 and 10−4 M). PPV (10−4 M)- and SNP (10−4 M)-induced maximal relaxations were greater in broilers than in Leghorns (176.2 ± 14.7 vs. 120.9 ± 14.7% and 201.3 ± 7.8 vs. 171.2 ± 10.7%, respectively, P < 0.05). Broiler PA rings appear to have increased intrinsic tone and reduced endothelium-derived nitric oxide activity, both of which may contribute to the susceptibility of broiler chickens to pulmonary hypertension.
Early phase insulin infusion and muscarinic blockade in obese and lean subjects
Authors: Teff Karen L. , Townsend Raymond R.
Published: December 2017

The effect of early phase insulin on postprandial levels of insulin, C-peptide, glucose, and glucagon was investigated in lean ( n = 10) and obese ( n = 12) subjects. Subjects underwent four conditions during ingestion of a meal (600 kcal): 1) saline infusion; 2) 10-min insulin infusion simultaneously with meal ingestion (0.24 U bolus, 15 mU ⋅ m−2 ⋅ min−1); 3) atropine infusion (0.4 mg/m2 bolus, 0.4 mg ⋅ m−2 ⋅ h for 4 h); 4) insulin and atropine infusion. Blood samples were taken for 3.5 h. Insulin infusion had no effect on postprandial insulin levels in either population but significantly reduced postprandial glucose in the obese subjects ( P < 0.05). Obese subjects with elevated postprandial glucose levels in the presence of muscarinic blockade exhibited a decline in glucose with insulin supplementation. Atropine reduced postprandial insulin levels in both groups, with a greater attenuation in the obese ( P< 0.01), but postprandial glucose levels were also significantly reduced, suggesting that atropine inhibited gastric emptying. Thus the effects of muscarinic blockade on postprandial insulin levels cannot be evaluated. These data suggest that insulin supplementation during the preabsorptive time period may contribute to glucoregulation in the obese population.
Impaired osmoregulatory responses in rats with area postrema lesions
Authors: Curtis Kathleen S. , Huang Wan , Sved Alan F. , Verbalis Joseph G. , Stricker Edward M.
Published: December 2017

Area postrema lesions (APX) in adult male rats produced a robust spontaneous intake of 0.5 M NaCl, as reported previously. The largest NaCl intakes (up to 108 ml/day) were observed when there was little incidental damage in the medial subnucleus of the nucleus of the solitary tract adjacent to the caudal and middle portions of the area postrema. Rats with discrete APX also drank substantial amounts of 0.5 M NaCl when access to saline was restricted to 7 h/day (up to 30 ml in 1 h, 48 ml in 7 h). Such large NaCl intakes stimulated considerable water ingestion and renal sodium excretion, but together these responses usually were insufficient for osmoregulation during the 7-h test period. After systemic administration of hypertonic NaCl solution, rats with APX excreted less Na+ in urine and secreted less vasopressin and oxytocin than control rats did. The prominent salt appetite, insufficient thirst and natriuresis in response to an ingested NaCl load, and blunted natriuresis and neurohypophysial hormone secretion in response to an injected NaCl load, all indicate that osmoregulatory responses are impaired in rats after APX.
Role of Ca2+channels in NE-induced increase in [Ca2+]iand tension in fetal and adult cerebral arteries
Authors: Long Wen , Zhao Yu , Zhang Lubo , Longo Lawrence D.
Published: December 2017

In vascular smooth muscle, elevation of agonist-induced intracellular Ca2+concentration ([Ca2+]i) occurs via both Ca2+release from intracellular stores and Ca2+influx across the plasma membrane. In the cerebral vasculature of the fetus and adult the relative roles of these mechanisms have not been defined. To test the hypothesis that plasma membrane L-type and receptor-operated Ca2+channels play a key role in NE-induced vasoconstriction via alterations in plasma membrane Ca2+flux and that this may change with developmental age, we performed the following study. In main branch middle cerebral arteries (MCA) from near-term fetal (∼140 days) and nonpregnant adult sheep, we quantified NE-induced responses of vascular tension and [Ca2+]i(by use of fura 2) under standard conditions in response to several Ca2+channel blockers and in response to zero extracellular Ca2+. In fetal and adult MCA, maximal NE-induced tensions (g) were 0.91 ± 0.12 ( n = 10) and 1.61 ± 0.13 ( n = 12), respectively. The pD2values for NE-induced tension were both 6.0 ± 0.1, whereas the fetal and adult maximum responses (%Kmax) were 107 ± 16 and 119 ± 7, respectively. The fetal and adult pD2values for NE-induced increase of [Ca2+]iwere 6.2 ± 0.1 and 6.4 ± 0.1, respectively, whereas maximum [Ca2+]iresponses were 81 ± 9 and 103 ± 15% of Kmax, respectively. After 10−5M NE-induced contraction, nifedipine resulted in dose-dependent decrease in vessel tone and [Ca2+]iwith pIC50values for fetal and adult tensions of 7.3 ± 0.1 and 6.6 ± 0.1, respectively ( P < 0.01; n = 4 each), whereas pIC50for [Ca2+]iresponses were 7.2 ± 0.1 and 6.9 ± 0.1, respectively. The pIC50values for tension for diltiazem and verapamil were somewhat lower but showed a similar relationship. The receptor-operated Ca2+channel blocker 2-nitro-4 carboxyphenyl- N,N-diphenyl carbamate showed little effect on NE-induced vessel contractility or [Ca2+]i. In the absence of extracellular Ca2+for 2 min, 10−5M NE resulted in markedly attenuated responses of adult MCA tension and [Ca2+]ito 39 ± 7 and 73 ± 8% of control values ( n = 4). For fetal MCA, exposure to extracellular Ca2+concentration resulted in essentially no contractile or [Ca2+]iresponse ( n = 4). Similar blunting of NE-induced tension and [Ca2+]iwas seen in response to 10−3M lanthanum ion. These findings provide evidence to suggest that especially in fetal, but also in adult, ovine MCA, Ca2+flux via L-type calcium channels plays a key role in NE-induced contraction. In contrast, Ca2+flux via receptor-operated Ca2+channels is of less importance. This developmental difference in the role of cerebrovascular plasma membrane Ca2+channels may be an important association with increased Ca2+sensitivity of the fetal vessels.
2-Mercaptoacetate, an inhibitor of fatty acid oxidation, decreases the membrane potential in rat liver in vivo
Authors: Boutellier Sandra , Lutz Thomas A. , Volkert Matthias , Scharrer Erwin
Published: December 2017

In former work, intraperitoneal injection of 2-mercaptoacetate (MA), an inhibitor of fatty acid oxidation, increased food intake in rats, which was attenuated by hepatic branch vagotomy, and intraportal injection of MA increased the discharge rate in hepatic vagal afferents. In the present study, we investigated, whether intraperitoneal injection or intraportal infusion of MA affects the hepatic membrane potential in rats in vivo. The liver cell membrane potential was measured in anesthetized Sprague-Dawley rats with the microelectrode technique. Intraperitoneal injection of MA at a dose of 800 μmol/kg body wt significantly decreased the hepatocyte membrane potential by 3.8 mV, whereas at a dose of 400 μmol/kg, the depolarization (1.5 mV) of the membrane was not significant. In another strain of Sprague-Dawley rats, however, MA (400 μmol/kg) produced a significant depolarization of the hepatocyte membrane 50 min (2.6 mV) and 2 h (2.9 mV) after intraperitoneal injection. Intraportal infusion of MA (400 μmol/kg) significantly depolarized the membrane 20 and 50 min after infusion by 3.3 and 4.1 mV, respectively. MA at a dose of 800 μmol/kg also depolarized the membrane (4.8 mV after 50 min). These findings in principle are consistent with the “potentiostatic” hypothesis, postulating a link between the hepatic membrane potential, afferent vagal activity, and the control of food intake.
Heat acclimation and hypohydration: involvement of central angiotensin II receptors in thermoregulation
Authors: Horowitz Michal , Kaspler Pavel , Simon Eckhart , Gerstberger Ruediger
Published: December 2017

This investigation attempted to confirm the involvement of central ANG II-ergic signals in thermoregulation. Experiments were conducted on rats undergoing short (STHA)- and long (LTHA)-term heat acclimation, with and without superimposed hypohydration. Vasodilatation (VTsh) and salivation (STsh) temperature thresholds, tail blood flow, and heat endurance were measured in conscious rats during heat stress (40°C) before and after losartan (Los), an ANG II AT1-selective receptor antagonist, administration either to the lateral ventricle or intravenously. Heat acclimation alone resulted in decreased VTsh. STsh decreased during STHA and resumed the preacclimation value, together with markedly increased heat endurance on LTHA. Hypohydration did not affect this biphasic response, although STsh was elevated in all groups. The enhanced heat endurance attained by LTHA was blunted. Neither Los treatment affected the nonacclimated rats. In the heat-acclimated, euhydrated rats, intracerebroventricular Los resulted in decreased VTsh, whereas intravenous Los resulted in elevated STsh. Both intracerebroventricular and intravenous Los led to markedly enhanced heat endurance of the LTHA hypohydrated rats. It is concluded that the LTHA group showed a loss of the benefits acquired by acclimation on hypohydration, whereas the STHA rats, which show an accelerated autonomic excitability in that phase, gained some benefit. It is suggested that ANG II modulates thermoregulation in conditions of chronic adjustments. Central ANG II signals may lead to VTsh upshift, whereas circumventricular structures, activated via circulating ANG II, decrease STsh. On hypohydration these responses seem to be desensitized.
Nonlinear, fractal, and spectral analysis of the EEG of lizard,Gallotia galloti
Authors: González Julián , Gamundi Antoni , Rial Rubén , Nicolau M. Cristina , de Vera Luis , Pereda Ernesto
Published: December 2017

Electroencephalogram (EEG) from dorsal cortex of lizard Gallotia galloti was analyzed at different temperatures to test the presence of fractal or nonlinear structure during open (OE) and closed eyes (CE), with the aim of comparing these results with those reported for human slow-wave sleep (SWS). Two nonlinear parameters characterizing EEG complexity [correlation dimension (D2)] and predictability [largest Lyapunov exponent (λ1)] were calculated, and EEG spectrum and fractal exponent β were determined via coarse graining spectral analysis. At 25°C, evidence of nonlinear structure was obtained by the surrogate data test, with EEG phase space structure suggesting the presence of deterministic chaos (D2 ∼6, λ1∼1.5). Both nonlinear parameters were greater in OE than in CE and for the right hemisphere in both situations. At 35°C the evidence of nonlinearity was not conclusive and differences between states disappeared, whereas interhemispheric differences remained for λ1. Harmonic power always increased with temperature within the band 8–30 Hz, but only with OE within the band 0.3–7.5 Hz. Qualitative similarities found between lizard and human SWS EEG support the hypothesis that reptilian waking could evolve into mammalian SWS.
Suppression of PGE2fever at near term: reduced thermogenesis but not enhanced vasopressin antipyresis
Authors: Chen Xihua , Hirasawa Michiru , Takahashi Yoshimi , Landgraf Rainer , Pittman Quentin J.
Published: December 2017

Fevers are known to be suppressed near term in the mother, but the mechanism responsible for this phenomenon is not understood. We tested the hypothesis that the suppression of fever at term is a result of enhanced vasopressin-induced antipyresis. Effects of intracerebroventricular prostaglandin E2(PGE2) were examined in rats at gestational days 16–17 and 19–20 (near term) and days 1–2 postpartum. PGE2(50 ng) elevated body and interscapular brown adipose tissue (iBAT) temperatures and increased sympathetic nerve activity to the iBAT. PGE2-induced changes in iBAT temperature and nerve activity, as well as in rectal temperature, were reduced or eliminated near term, and responses were recovered in the postpartum period. Blood pressure and heart rate changes induced by central PGE2were also decreased at near term. Coinfusion of Manning compound, a V1vasopressin receptor antagonist, with PGE2throughout the peripartum period did not reverse the suppressed iBAT temperature and nerve activity or body temperature responses to PGE2. Microdialysis experiments revealed unchanged terminal release of vasopressin in the ventral septal area after PGE2infusion in either pregnant or parturient rats. These results suggest that fever reduction at near term is not associated with enhanced vasopressin antipyresis, but may be a result of reduced sympathetic tone and in particular a reduced sympathetic drive to the iBAT. This finding may reflect a generalized reduction in autonomic output around the time of parturition.
Use of NK1knockout mice to analyze substance P-induced edema formation
Authors: Cao Thong , Gerard Norma P. , Brain Susan D.
Published: December 2017

The mechanisms involved in tachykinin-induced neurokinin-1 (NK1) receptor-mediated edema formation have been studied in anesthetized wild-type and NK1knockout mice. Intradermally injected substance P (30–300 pmol), NK1agonists septide (3–30 pmol) and GR-73632 (3–30 pmol), and the mast cell-degranulating agent, compound 48/80 induced dose-dependent edema in wild-type skin, measured by the accumulation of intravenously injected125I-labeled albumin. Septide was 3–10× more potent than substance P. The tachykinins were inactive in knockout mice, but compound 48/80 induced a significantly greater edema ( P < 0.05) than that observed in paired wild-type mice. Capsaicin (which releases endogenous neuropeptides) and exogenous tachykinins induced edema formation, which was reduced by the mast cell amine histamine H1antagonist mepyramine ( P < 0.05). These findings confirm that tachykinins mediate edema formation via the NK1receptor and provide direct evidence that the septide-sensitive binding site is on the NK1receptor. Furthermore, results suggest that edema induced by the tachykinins, although totally dependent on NK1receptor-mediated mechanism, contains a mast cell-dependent component. The evidence is in keeping with an NK1receptor on mast cells.
Effects of 17β-estradiol on the baroreflex control of sympathetic activity in conscious ovariectomized rats
Authors: He Xiao-Rui , Wang Weihua , Crofton Joan T. , Share Leonard
Published: December 2017

The effects of chronic treatment with 17β-estradiol on baroreflex control of sympathetic activity were examined in conscious unrestrained ovariectomized rats. Baroreflex function was evaluated by logistic sigmoidal analysis of the relationships between changes in mean arterial pressure (MABP) and changes in heart rate (HR) and splanchnic nerve activity (SNA) when MABP was rapidly increased to 150 mmHg by intravenous phenylephrine after its reduction to 50 mmHg by intravenous nitroprusside. These baroreflex function curves were similar in vehicle- and estradiol-treated rats. However, after a 30-min infusion of vasopressin in vehicle-treated rats, the curve for HR was shifted downward, and the upper plateau and maximum gain for the SNA curve were reduced. These effects were abolished by estradiol. A 30-min phenylephrine infusion had no effect on the baroreflex curves. Thus estrogen can modulate the action of vasopressin on baroreflex control of sympathetic outflow and thereby participate in cardiovascular regulation.
Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading
Authors: Carlson Christian J. , Booth Frank W. , Gordon Scott E.
Published: December 2017

Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S.-J. Lee. Nature 387: 83–90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation ( r = 0.725, P < 0.0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.
Salt-sensitive hypertension in ANP knockout mice is prevented by AT1 receptor antagonist losartan
Authors: Melo Luis G. , Veress Anthony T. , Chong Chee K. , Ackermann Uwe , Sonnenberg Harald
Published: December 2017

Mice harboring a functional deletion of the pro-atrial natriuretic peptide (ANP) gene (−/−) develop salt-sensitive hypertension relative to their wild-type (+/+) counterparts after prolonged (>1 wk) maintenance on high-salt (HS, 8% NaCl) diet. We reported recently that the sensitization of arterial blood pressure (ABP) to dietary salt in the −/− mice is associated with failure to downregulate plasma renin activity. To further characterize the role and mechanism of ANG II in the sensitization of ABP to salt in the ANP “knockout” mice, we measured ABP, heart rate (HR), and plasma catecholamine and aldosterone concentrations in −/− and +/+ mice maintained on HS for 4 wk and treated with daily injections of AT1 receptor antagonist DuP-753 (losartan) or distilled water (control). Daily food and water intake and fluid and electrolyte excretion were also measured during the first and last weeks of the dietary regimen. Cumulative urinary excretion of fluid and electrolytes did not differ significantly between genotypes and was not altered by chronic treatment with losartan. Basal ABP and HR were significantly elevated in control −/− mice compared with control +/+ mice. Losartan did not affect ABP or HR in +/+ mice, but reduced ABP and HR in the −/− mice to the levels in the +/+ mice. Total plasma catecholamine was elevated by approximately ten-fold in control −/− mice compared with control +/+ mice. Losartan reduced plasma catecholamine concentration significantly in −/− mice and abrogated the difference in plasma catecholamine between −/− and +/+ mice on HS diet. Plasma aldosterone did not differ significantly between genotypes and was not altered by losartan. We conclude that salt sensitivity of ABP in ANP knockout mice is mediated, at least in part, by a synergistic interaction between ANG II and sympathetic nerve activity.
Regional conductance changes during hemorrhage in pregnant and nonpregnant conscious rabbits
Authors: Brooks Virginia L. , Kane Colleen M. , Welch Lisa S.
Published: December 2017

Late pregnant (P) conscious rabbits are less able to maintain arterial pressure during hemorrhage than nonpregnant (NP) animals. This study tested the hypothesis that the difference is due in part to less reflex vasoconstriction when the rabbits are P. Rabbits ( n = 14) were instrumented with arterial and venous catheters as well as ultrasonic flow probes around the superior mesenteric, renal, and/or terminal aortic arteries. Pregnancy increased ( P < 0.05) blood volume [235 ± 5 (P) vs. 171 ± 3 (NP) ml], terminal aortic conductance [1.88 ± 0.11 (P) vs. 0.98 ± 0.06 (NP) ml ⋅ min−1 ⋅ mmHg−1], mesenteric conductance [1.20 ± 0.19 (P) vs. 0.80 ± 0.05 (NP) ml ⋅ min−1 ⋅ mmHg−1], and heart rate [191 ± 4 (P) vs. 162 ± 3 (NP) beats/min] and decreased arterial pressure [59 ± 1 (P) vs. 67 ± 2 (NP) mmHg; P < 0.05]. Renal conductance was unaltered. The rabbits were bled in both the NP and P states at 2% of the initial blood volume per minute until arterial pressure fell below 45 mmHg. Arterial pressure fell with less blood loss in P rabbits [28 ± 2% (P) vs. 39 ± 2% (NP) of initial blood volume; P < 0.001]. Terminal aortic conductance decreased ( P < 0.001) before the pressure fall in both groups, but the response was reduced in P rabbits. Mesenteric and renal conductances did not change in either group before the blood pressure fall. During the pressure fall, terminal aortic conductance increased ( P < 0.05) only in NP rabbits. Mesenteric conductance increased in both groups. In summary, rabbits in late gestation are less able to maintain arterial pressure during hemorrhage, at least in part because of reduced vasoconstriction in tissues perfused by the terminal aorta.
Tissue-specific changes in RNA synthesis in vivo during anoxia in crucian carp
Authors: Smith Richard W. , Houlihan Dominic F. , Nilsson Göran E. , Alexandre Julie
Published: December 2017

The overall energy budget for protein synthesis (i.e., transcription plus translation) is thought to consist of fixed and variable components, with RNA synthesis accounting for the former and protein synthesis the latter. During anoxia, the downregulation of protein synthesis (i.e., the variable component), to reduce energetic demand, is an important aspect of survival in crucian carp. The present study examines RNA synthesis during anoxia by labeling with [3H]uridine. A novel synthesis rate calculation is presented, which allows for the tissue-specific salvage of uridine, with synthesis rates finally expressed relative to DNA. After 48 h anoxia, the decline (29%) in brain RNA synthesis and increases in the heart and liver (132 and 871%, respectively) support known RNA functions during hypoxic/anoxic survival. This study provides evidence that, in an anoxia-tolerant species, survival mechanisms involving RNA are able to operate because tissue-specific restructuring of the RNA synthesis process enables fixed synthesis costs to be maintained; this may be as vital to survival as exploiting the variable energetic demand of protein synthesis.
Role of nitric oxide in intrarenal hemodynamics in experimental diabetes mellitus in rats
Authors: Pflueger Axel C. , Larson Timothy S. , Hagl Siegfried , Knox Franklyn G.
Published: December 2017

The role of nitric oxide (NO) in the regulation of the intrarenal microcirculation in streptozotocin (STZ)-induced diabetes mellitus in rats is not clear. We examined renal cortical and papillary hemodynamics in STZ rats and determined the effects of systemic inhibition and stimulation of NO synthesis. Renal blood flow in cortical (QCC), and inner medullary ascending (QAV) and descending (QDV) vasa recta capillaries was measured by fluorescence videomicroscopy in STZ Munich-Wistar rats and nondiabetic control rats. Ten days after STZ injection (80 mg/kg ip), basal QCCand QDVwere significantly greater in STZ rats ( n = 16) compared with control rats ( n = 15). Infusion of NG-monomethyl-l-arginine (l-NMMA, 15 mg/kg bolus, 500 μg ⋅ min−1⋅ kg−1iv) decreased QCC(−41%), QAV(−38%), and QDV(−37%) in control rats ( n = 6) and to a significantly greater magnitude than in STZ rats ( n = 7), QCC(−14%), QAV(−20%), and QDV(−25%). Coinfusion ofl-arginine (l-Arg, 1 mg ⋅ kg−1⋅ min−1iv) with l-NMMA increased QCCto a significantly greater extent ( P < 0.01) in control rats compared with STZ rats. In subsequent studies, infusion ofl-Arg alone increased QCC(+50%), QAV(+16%), and QDV(+11%) in control rats ( n = 5) but had no effect in STZ rats ( n = 5). These results show that the response of renal cortical and papillary capillary blood flow to both inhibition and stimulation of NO synthesis is attenuated in the early onset of STZ-diabetes mellitus rats compared with control rats.
Cardiovascular afferent signals and drinking in response to hypotension in dogs
Authors: Thrasher Terry N. , Keenan Craig R. , Ramsay David J.
Published: December 2017

Arterial hypotension stimulates increases in plasma arginine vasopressin (AVP), plasma renin activity (PRA), and water intake in conscious dogs. We have previously reported that increasing left atrial but not right atrial pressure completely blocks the increase in plasma AVP and PRA induced by hypotension. The goal of the present study was to examine the effect of increasing right or left atrial pressure on water intake induced by arterial hypotension. Dogs were prepared with occluding cuffs on the thoracic inferior vena cava, the pulmonary artery, and the ascending aorta. We reduced mean arterial pressure (MAP) 25% below control by either inferior vena cava constriction (IVCC), pulmonary artery constriction (PAC), or ascending aorta constriction (AAC) and measured water intake over a 2-h period. Cumulative water intake during IVCC ( n = 6) and PAC ( n = 6) was 7.8 ± 2.0 and 6.7 ± 2.6 ml/kg, respectively. There was no difference between either the latency or the volume consumed between the two treatments. In contrast, none of the dogs drank during hypotension induced by AAC ( n = 5). Because the degree of arterial baroreceptor unloading was the same in each treatment by design, we conclude that stimulation of left atrial receptors inhibits drinking in response to arterial hypotension but that stimulation of right atrial receptors has no effect on the response in dogs.
Heart rate surges during REM sleep are associated with theta rhythm and PGO activity in cats
Authors: Rowe Katharine , Moreno Ricardo , Lau T. Rern , Wallooppillai Umesha , Nearing Bruce D. , Kocsis Bernat , Quattrochi James , Hobson J. Allan , Verrier Richard L.
Published: December 2017

Rapid eye movement (REM) sleep is characterized by periods of profound cardiac autonomic activation evident in heart rate surges in humans and canines. Our goals were to determine whether or not the heart rate surge phenomenon occurs in cats and to characterize concurrent central nervous system activity. Cortical and hippocampal electroencephalogram, electromyogram, electrooculogram, pontogeniculooccipital (PGO) waves, subcutaneous electrocardiogram, and respiration were recorded. Bouts of sinus tachycardia lasting ≥3.5 s achieved a rate of 210 beats/min and were present predominantly during REM sleep. Heart rate during the surges rose an average of 26.4% from 132.5 ± 2.0 beats/min before the surge to 167.5 ± 2.6 beats/min ( P< 0.001) and returned to 130.7 ± 2.6 beats/min ( P < 0.001). The heart rate surges were invariably accompanied by increased incidence and frequency of hippocampal theta waves and increased PGO wave frequency and incidence of PGO wave clusters and eye movement clusters. The occurrence of surges was dramatically reduced from 0.11 ± 0.03 to 0.01 ± 0.01/15 s of REM sleep ( P = 0.02) by atenolol (0.6 mg/kg iv), indicating that the phenomenon is β1-adrenergically mediated. These findings suggest a coupling between central activation of cardiac sympathetic nerves and the generation of hippocampal theta waves and PGO activity.
Early kidney TNF-α expression mediates neutrophil infiltration and injury after renal ischemia-reperfusion
Authors: Donnahoo Kirstan K. , Meng Xianzhong , Ayala Alfred , Cain Mark P. , Harken Alden H. , Meldrum Daniel R.
Published: December 2017

The purpose of this study was to determine whether isolated renal ischemia and reperfusion (I/R) induces renal tumor necrosis factor (TNF) mRNA production, TNF protein expression, or TNF bioactivity and, if so, whether local/early TNF production acts as mediator of ischemia-induced, neutrophil-mediated renal injury. After rats were anesthetized, varying periods of renal ischemia, with or without reperfusion, were induced. Kidney mRNA content (RT-PCR), TNF protein expression (ELISA), TNF bioactivity (WEHI-164 cell clone cytotoxicity assay), and neutrophil infiltration [myeloperoxidase (MPO) assay] were determined. In other animals, renal MPO and serum creatinine were assessed after TNF was neutralized [binding protein (TNF-BP)]. Thirty minutes of ischemia induced renal TNF mRNA. TNF protein expression and bioactivity peaked after 1 h ischemia and 2 h reperfusion, whereas neutrophil infiltration peaked at 4 h reperfusion. TNF-BP neutralized TNF bioactivity, reduced neutrophil infiltration, and protected postischemic function. These results constitute the initial demonstration that 1) early renal tissue TNF expression contributes to neutrophil infiltration and injury after I/R and 2) TNF-BP may offer a new adjunctive therapy in renal preservation prior to planned ischemic insults.