bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypercapnia-induced cerebral and ocular vasodilation is not altered by glibenclamide in humans
Authors: Bayerle-Eder Michaela , Wolzt Michael , Polska Elzbieta , Langenberger Herbert , Pleiner Johannes , Teherani Daniela , Rainer Georg , Polak Kaija , Eichler Hans-Georg , Schmetterer Leopold
Published: December 2017

Carbon dioxide is an important regulator of vascular tone. Glibenclamide, an inhibitor of ATP-sensitive potassium channel (KATP) activation, significantly blunts vasodilation in response to hypercapnic acidosis in animals. We investigated whether glibenclamide also alters the cerebral and ocular vasodilator response to hypercapnia in humans. Ten healthy male subjects were studied in a controlled, randomized, double-blind two-way crossover study under normoxic and hypercapnic conditions. Glibenclamide (5 mg po) or insulin (0.3 mU ⋅ kg− 1 ⋅ min− 1iv) were administered with glucose to achieve comparable plasma insulin levels. In control experiments, five healthy volunteers received glibenclamide (5 mg) or nicorandil (40 mg) or glibenclamide and nicorandil in a randomized, three-way crossover study. Mean blood flow velocity and resistive index in the middle cerebral artery (MCA) and in the ophthalmic artery (OA) were measured with Doppler sonography. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation. Forearm blood flow was measured with venous occlusion plethysmography. Hypercapnia increased ocular fundus pulsation amplitude by +18.2–22.3% ( P < 0.001) and mean flow velocity in the MCA by +27.4–33.3% ( P < 0.001), but not in the OA (2.1–6.5%, P = 0.2). Forearm blood flow increased by 78.2% vs. baseline ( P = 0.041) after nicorandil administration. Glibenclamide did not alter hypercapnia-induced changes in cerebral or ocular hemodynamics and did not affect systemic hemodynamics or forearm blood flow but significantly increased glucose utilization and blunted the nicorandil-induced vasodilation in the forearm. This suggests that hypercapnia-induced changes in the vascular beds under study are not mediated by activation of KATPchannels in humans.
Vestibular stimulation leads to distinct hemodynamic patterning
Authors: Kerman I. A. , Emanuel B. A. , Yates B. J.
Published: December 2017

Previous studies demonstrated that responses of a particular sympathetic nerve to vestibular stimulation depend on the type of tissue the nerve innervates as well as its anatomic location. In the present study, we sought to determine whether such precise patterning of vestibulosympathetic reflexes could lead to specific hemodynamic alterations in response to vestibular afferent activation. We simultaneously measured changes in systemic blood pressure and blood flow (with the use of Doppler flowmetry) to the hindlimb (femoral artery), forelimb (brachial artery), and kidney (renal artery) in chloralose-urethane-anesthetized, baroreceptor-denervated cats. Electrical vestibular stimulation led to depressor responses, 8 ± 2 mmHg (mean ± SE) in magnitude, that were accompanied by decreases in femoral vasoconstriction (23 ± 4% decrease in vascular resistance or 36 ± 7% increase in vascular conductance) and increases in brachial vascular tone (resistance increase of 10 ± 6% and conductance decrease of 11 ± 4%). Relatively small changes (<5%) in renal vascular tone were observed. In contrast, electrical stimulation of muscle and cutaneous afferents produced pressor responses (20 ± 6 mmHg) that were accompanied by vasoconstriction in all three beds. These data suggest that vestibular inputs lead to a complex pattern of cardiovascular changes that is distinct from that which occurs in response to activation of other types of somatic afferents.
Hindbrain serotonin and the rapid induction of sodium appetite
Authors: Menani José Vanderlei , De Luca Laurival Antonio , Thunhorst Robert L. , Johnson Alan Kim
Published: December 2017

Both systemically administered furosemide and isoproterenol produce water intake (i.e., thirst). Curiously, however, in light of the endocrine and hemodynamic effects produced by these treatments, they are remarkably ineffective in eliciting intake of hypertonic saline solutions (i.e., operationally defined as sodium appetite). Recent work indicates that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nuclei (LPBN) markedly enhance a preexisting sodium appetite. The present studies establish that a de novo sodium appetite can be induced with LPBN-methysergide treatment under experimental conditions in which only water is typically ingested. The effects of bilateral LPBN injections of methysergide were studied on the intake of water and 0.3 M NaCl following acute (beginning 1 h after treatment) diuretic (furosemide)-induced sodium and water depletion and following subcutaneous isoproterenol treatment. With vehicle injected into the LPBN, furosemide treatment and isoproterenol injection both caused water drinking but essentially no intake of hypertonic saline. In contrast, bilateral treatment of the LPBN with methysergide induced the intake of 0.3 M NaCl after subcutaneous furosemide and isoproterenol. Water intake induced by subcutaneous furosemide or isoproterenol was not changed by LPBN-methysergide injections. The results indicate that blockade of LPBN-serotonin receptors produces a marked intake of hypertonic NaCl (i.e., a de novo sodium appetite) after furosemide treatment as well as subcutaneous isoproterenol.
Receptor subtypes mediating depressor responses to microinjections of nicotine into medial NTS of the rat
Authors: Dhar S. , Nagy F. , McIntosh J. M. , Sapru H. N.
Published: December 2017

Microinjections (50 nl) of nicotine (0.01–10 μM) into the nucleus of the solitary tract (NTS) of adult, urethan-anesthetized, artificially ventilated, male Wistar rats, elicited decreases in blood pressure and heart rate. Prior microinjections of α-bungarotoxin (α-BT) and α-conotoxin ImI (specific toxins for nicotinic receptors containing α7 subunits) elicited a 20–38% reduction in nicotine responses. Similarly, prior microinjections of hexamethonium, mecamylamine, and α-conotoxin AuIB (specific blockers or toxin for nicotinic receptors containing α3β4 subunits) elicited a 47–79% reduction in nicotine responses. Nicotine responses were completely blocked by prior sequential microinjections of α-BT and mecamylamine into the NTS. Complete blockade of excitatory amino acid receptors (EAARs) in the NTS did not attenuate the responses to nicotine. It was concluded that 1) the predominant type of nicotinic receptor in the NTS contains α3β4 subunits, 2) a smaller proportion contains α7 subunits, 3) the presynaptic nicotinic receptors in the NTS do not contribute to nicotine-induced responses, and 4) EAARs in the NTS are not involved in mediating responses to nicotine.
Enhanced sarcoplasmic reticulum Ca2+release following intermittent sprint training
Authors: Ørtenblad Niels , Lunde Per K. , Levin Klaus , Andersen Jesper L. , Pedersen Preben K.
Published: December 2017

To evaluate the effect of intermittent sprint training on sarcoplasmic reticulum (SR) function, nine young men performed a 5 wk high-intensity intermittent bicycle training, and six served as controls. SR function was evaluated from resting vastus lateralis muscle biopsies, before and after the training period. Intermittent sprint performance (ten 8-s all-out periods alternating with 32-s recovery) was enhanced 12% ( P < 0.01) after training. The 5-wk sprint training induced a significantly higher ( P < 0.05) peak rate of AgNO3-stimulated Ca2+release from 709 (range 560–877; before) to 774 (596–977) arbitrary units Ca2+⋅ g protein−1⋅ min−1(after). The relative SR density of functional ryanodine receptors (RyR) remained unchanged after training; there was, however, a 48% ( P < 0.05) increase in total number of RyR. No significant differences in Ca2+uptake rate and Ca2+-ATPase capacity were observed following the training, despite that the relative density of Ca2+-ATPase isoforms SERCA1 and SERCA2 had increased 41% and 55%, respectively ( P < 0.05). These data suggest that high-intensity training induces an enhanced peak SR Ca2+release, due to an enhanced total volume of SR, whereas SR Ca2+sequestration function is not altered.
Differential pattern of spinal sympathetic outflow in response to stimulation of the caudal medullary raphe
Authors: Larsen Peter D. , Zhong Sheng , Gebber Gerard L. , Barman Susan M.
Published: December 2017

In urethan-anesthetized cats, frequency domain analysis was used to explore the mechanisms of differential responses of inferior cardiac (CN), vertebral (VN), and renal (RN) sympathetic nerves to electrical stimulation of a discrete region of the medullary raphe (0–2 mm caudal to the obex). Raphe stimulation in baroreceptor-denervated cats at frequencies (7–12 Hz) that entrained the 10-Hz rhythm in nerve activity decreased CN and RN activities but increased VN activity. The reductions in CN and RN discharges were associated with decreased low-frequency (≤6 Hz) power and either increased (low stimulus intensity) or decreased (high stimulus intensity) 10-Hz band power. In contrast, VN 10-Hz band power was increased at all stimulus intensities, without changes in low-frequency power. High-frequency (25 Hz) stimulation decreased low-frequency activity of CN and RN discharges in both baroreceptor-denervated and baroreceptor-intact cats, without decreasing VN low-frequency activity. We propose that the differential pattern produced by raphe stimulation involves resonance at the level of the 10-Hz oscillators and differential inhibition of follower circuits that transmit both 10-Hz and low-frequency activity to sympathetic nerves.
Effects of chronic reduction in uterine blood flow on fetal and placental growth in the sheep
Authors: Lang Uwe , Baker R. Scott , Khoury Jane , Clark Kenneth E.
Published: December 2017

Pregnancy is associated with a significant increase in uteroplacental blood flow (UBF), which is responsible for delivering adequate nutrients and oxygen for fetal and placental growth. The present study was designed to determine the effects of vascular insufficiency on fetal and placental growth. Thirty-nine late-term pregnant ewes were instrumented to investigate the effects of chronic UBF reduction. Animals were split into three groups based on uterine blood flow, and all animals were killed on gestational day 138. UBF, which began at 851 ± 74 ml/min ( n = 39), increased in controls (C) to 1,409 ± 98 ml/min ( day 138 of gestation) and in the moderately restricted (RM) group to 986 ± 69 ml/min. In the severely restricted (RS) group, UBF was only 779 ± 79 ml/min on gestational day 138. This reduction in UBF significantly affected fetal body weight with RMfetuses weighing 3,685 ± 178 g and RS fetuses weighing 2,920 ± 164 g compared with C fetal weights of 4,318 ± 208 g. Fetal brain weight was not affected, whereas ponderal index was significantly reduced in RM (2.94 ± 0.09) and RS fetuses (2.49 ± 0.08) compared with the value of the C fetuses (3.31 ± 0.08). Placental weight was also significantly reduced in the RM group, being 302 ± 24 g, whereas the RS group placenta weighed 274 ± 61 g compared with the C values of 414 ± 57 g. Fetal heart, liver, lung, and thymus were all significantly smaller in the RS group. Thus the present study shows a clear relationship between the level of UBF and both fetal and placental size. Furthermore, the observation that fetal brain weight was not affected, whereas fetal body weight was significantly reduced suggests that this experimental preparation may provide a useful model in which to study asymmetric fetal growth restriction.
Changes in cardiac mechanics with heat acclimation: adrenergic signaling and SR-Ca regulatory proteins
Authors: Mirit Eynan , Gross Chaya , Hasin Yonathan , Palmon Aharon , Horowitz Michal
Published: December 2017

The involvement of adrenergic signaling and sarcoplasmic calcium regulatory proteins in the development of heat acclimation-induced adaptations in cardiac mechanics was studied in heat-acclimated (34°C) rats for 2, 5, and 30 days (AC2, AC5, and AC30, respectively). Control (C) rats were held at 24 ± 1°C. Systolic pressure (LVP) and velocities of contraction (dP/d t/P) and relaxation (−dP/d t/P) were measured using a Langendorff system. For adrenergic signaling, β-adrenoreceptor (AR) density and affinity (Scatchard plots) and cardiac inotropic response to norepinephrine (10−7mM, ± 10−6mM propranolol) were measured. For the regulatory proteins, steady-state levels of Ca2+-ATPase and phospholamban (PLB) mRNAs and the encoded proteins Ca2+-ATPase [sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)] and PLB were measured using semiquantitative RT-PCR and Western immunoblotting, respectively. Both short (STHA; AC2and AC5)- and long-term heat acclimation (LTHA; AC30) enhanced LVP. However, dP/d t ⋅ P and −dP/d t ⋅ P in STHA hearts resembled that of the controls, whereas on LTHA, both parameters decreased ( P< 0.05), implying decreased velocity of contraction and relaxation. β-AR density remained unchanged with their affinity markedly decreased ( P < 0.05). AR responsiveness, however, diminished in AC2but was markedly enhanced on LTHA. During STHA, PLB and sarcoplasmic reticulum Ca2+-ATPase transcripts were upregulated with no change in the encoded proteins except for SERCA downregulation on AC5, leading to an increased PLB/SERCA ratio ( P < 0.05). This mismatched preacclimation lusitropic state on STHA and increased PLB/SERCA ratio was evident ( P < 0.05) due to downregulation of SERCA and upregulation of PLB. Our data fit a biphasic acclimation model in which desensitized adrenergic signaling is dominant during STHA, whereas on LTHA, the contractile machinery is influenced by altered expression of the calcium regulatory proteins leading to both augmented adrenergic inotropic response (via PLB elevation) and decreased velocity of relaxation. The sustained low thyroxin measured on LTHA causally associates with this response.
Role of potassium channels in catecholamine secretion in the rat adrenal gland
Authors: Nagayama Takahiro , Fukushima Yasuo , Yoshida Makoto , Suzuki-Kusaba Mizue , Hisa Hiroaki , Kimura Tomohiko , Satoh Susumu
Published: December 2017

We elucidated the functional contribution of K+channels to cholinergic control of catecholamine secretion in the perfused rat adrenal gland. The small-conductance Ca2+-activated K+(SKCa)-channel blocker apamin (10–100 nM) enhanced the transmural electrical stimulation (ES; 1–10 Hz)- and 1,1-dimethyl-4-phenyl-piperazinium (DMPP; 5–40 μM)-induced increases in norepinephrine (NE) output, whereas it did not affect the epinephrine (Epi) responses. Apamin enhanced the catecholamine responses induced by acetylcholine (6–200 μM) and methacholine (10–300 μM). The putative large-conductance Ca2+-activated K+channel blocker charybdotoxin (10–100 nM) enhanced the catecholamine responses induced by ES, but not the responses induced by cholinergic agonists. Neither the KAchannel blocker mast cell degranulating peptide (100–1000 nM) nor the KVchannel blocker margatoxin (10–100 nM) affected the catecholamine responses. These results suggest that SKCachannels play an inhibitory role in adrenal catecholamine secretion mediated by muscarinic receptors and also in the nicotinic receptor-mediated secretion of NE, but not of Epi. Charybdotoxin-sensitive Ca2+-activated K+channels may control the secretion at the presynaptic site.
Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women
Authors: Moon Jae-Hak , Nakata Ritsuko , Oshima Syunji , Inakuma Takahiro , Terao Junji
Published: December 2017

Quercetin is a typical flavonoid present mostly as glycosides in plant foods; it has attracted much attention for its potential beneficial effects in disease prevention. In this study, we examined human volunteers after the short-term ingestion of onion, a vegetable rich in quercetin glucosides. The subjects were served diets containing onion slices (quercetin equivalent: 67.6–93.6 mg/day) with meals for 1 wk. Quercetin was only found in glucuronidase-sulfatase-treated plasma, and its concentration after 10 h of fasting increased from 0.04 ± 0.04 μM before the trial to 0.63 ± 0.72 μM after the 1-wk trial. The quercetin content in low-density lipoprotein (LDL) after glucuronidase-sulfatase treatment corresponded to <1% of the α-tocopherol content. Human LDL isolated from the plasma after the trial showed little improvement of its resistance to copper ion-induced oxidation. It is therefore concluded that conjugated metabolites of quercetin accumulate exclusively in human blood plasma in the concentration range of 10−7 ∼ 10−6 M after the short-term ingestion of vegetables rich in quercetin glucosides, although these metabolites are hardly incorporated into plasma LDL.
Cardiovascular actions of centrally and peripherally administered trout urotensin-I in the trout
Authors: Mimassi Nagi , Shahbazi Fatemeh , Jensen Jörgen , Mabin Dominique , Conlon J. Michael , Le Mével Jean-Claude
Published: December 2017

The cardiovascular effects of centrally and peripherally administered synthetic trout urotensin (U)-I, a member of the corticotropin-releasing hormone family of neuroendocrine peptides, were investigated in unanesthetized rainbow trout Oncorhynchus mykiss. Intracerebroventricular injections of U-I (5.0 and 12.5 pmol) produced a sustained increase in mean dorsal aortic blood pressure (PDA) without significant change in heart rate (HR). This elevation in PDAwas associated with an increase in cardiac output, but systemic vascular resistance did not change. Intra-arterial injection of U-I (12.5–500 pmol) evoked a dose-dependent increase in PDA, but in contrast to the hemodynamic effects of centrally administered U-I, the hypertensive effect was associated with an increase in systemic vascular resistance and an initial fall in cardiac output. HR did not change or underwent a delayed increase. Pretreatment of trout with prazosin, an α-adrenoreceptor antagonist, completely abolished the rise in arterial blood pressure after intra-arterial administration of U-I, which was replaced by a sustained hypotension and tachycardia. Trout U-I produced a dose-dependent (pD2= 7.74 ± 0.08) relaxation of preconstricted rings of isolated trout arterial vascular smooth muscle, suggesting that the primary action of the peptide in the periphery is vasorelaxation that is rapidly reversed by release of catecholamines. Our results suggest that U-I may regulate blood pressure in trout by acting centrally as a neurotransmitter and/or neuromodulator and peripherally as a neurohormone functioning either as a locally acting vasodilator or as a potent secretagogue of catecholamines.
Novel expression and regulation of the renin-angiotensin system in metanephric organ culture
Authors: Norwood Victoria F. , Garmey Marjorie , Wolford Jeffrey , Carey Robert M. , Gomez R. Ariel
Published: December 2017

To evaluate the presence and regulation of the renin-angiotensin system (RAS) in metanephric organ culture, embryonic day 14 (E14) rat metanephroi were cultured for 6 days. mRNAs for renin and both ANG II receptors (AT1and AT2) are expressed at E14, and all three genes continue to be expressed in culture. Renin mRNA is localized to developing tubules and ureteral branches in the cultured explants. At E14, renin immunostaining is found in isolated cells scattered within the mesenchyme. As differentiation progresses, renin localizes to the ureteric epithelium, developing tubules and glomeruli. E14 metanephroi contain ANG II, and peptide production persists in culture. Renin activity is present at E14 (6.13 ± 0.61 pg ANG I · kidney−1· h−1) and in cultured explants (28.84 ± 1.13 pg ANG I · kidney−1· h−1). Renin activity in explants is increased by ANG II treatment (70.1 ± 6.36 vs. 40.97 ± 1.94 pg ANG I · kidney−1· h−1in control). This increase is prevented by AT1blockade, whereas AT2antagonism has no effect. These studies document an operational local RAS and a previously undescribed positive-feedback mechanism for renin generation in avascular, cultured developing metanephroi. This novel expression pattern and regulatory mechanism highlight the unique ability of developing renal cells to express an active RAS.
Parasympathetic reflex vasodilatation in rat submandibular gland
Authors: Mizuta Kentaro , Karita Keishiro , Izumi Hiroshi
Published: December 2017

The present study was designed to investigate 1) whether parasympathetic reflex vasodilatation occurs in the submandibular gland (SMG) in deeply urethan-anesthetized, cervically vagotomized, and sympathectomized rats when the central cut end of the lingual nerve (LN) is electrically stimulated and 2) to what extent the neural mechanisms underlying such responses are the same as those involved in the response to direct stimulation of the chorda-LN (CLN). Stimulation of each nerve separately elicited a marked blood flow increase in SMG. Section of the chorda tympani abolished the SMG blood flow response but had no effect on the lip blood flow increase evoked by LN stimulation. Section of the CLN abolished the SMG blood flow increases evoked by stimulation of either nerve. The SMG blood flow increases (regardless of whether they were evoked by LN or CLN stimulation) were markedly reduced by the autonomic cholinergic ganglion blocker hexamethonium. The present study demonstrates that a parasympathetic reflex vasodilator mechanism is present in the rat SMG and that it can express its effects under deep general anesthesia.
Bilateral distribution of vagal motor and sensory nerve fibers in the rat's lungs and airways
Authors: Fontán J. Julio Pérez , Diec Catherine T. , Velloff Christine R.
Published: December 2017

This study combined single and transneuronal labeling to define the origin of midline-crossing vagal fibers projecting to the rat's lungs. Injections of the β-subunit of cholera toxin (CT-β) into the lungs labeled similar numbers of neuronal somata in the nucleus ambiguus and dorsal motor nucleus of the vagus on both sides of the medulla, even though vagal stimulation increased lung resistance 50% less in the contralateral than in the ipsilateral lung. Unilateral cervical vagotomy prevented CT-β labeling of ipsilateral neuronal somata and sensory fibers, indicating that lung-bound vagal fibers undergo decussation only inside the thorax. Injections of CT-β and FluoroGold into opposite main stem bronchi double labeled 30% and 11% of all neuronal somata immunoreactive for CT-β and FluoroGold, respectively, showing that one single vagal motoneuron can innervate airways on both sides. Injections of pseudorabies virus into the right lung revealed a bilateral network of infected neurons, even after unilateral vagotomy. The latter did not prevent infection of the ipsilateral vagal nuclei. These findings demonstrate that vagal motoneurons that project to the lungs receive contralateral inputs from the airway premotor network and vagal bronchomotor centers.
IGF-I treatment attenuates renal abnormalities induced by neonatal ACE inhibition
Authors: Nilsson Annika B. M. , Nitescu Nicoleta , Chen Yun , Guron Gregor S. , Marcussen Niels , Matejka Göran L. , Friberg Peter
Published: December 2017

An intact renin-angiotensin system (RAS) during nephrogenesis is essential for normal renal development. We have shown previously that neonatal inhibition of the RAS, either with ANG II type 1-receptor blockade or angiotensin-converting enzyme (ACE) inhibition, induces irreversible renal abnormalities. The aim of the present study was to investigate whether an interrupted RAS can be compensated for by exogenous administration of another important renal growth-promoting factor, the insulin-like growth factor-I (IGF-I). Rats were treated daily with either the ACE inhibitor enalapril (10 mg/kg), recombinant human IGF-I (3 mg/kg), or the combination enalapril + IGF-I from perinatal day 3 to 13. Urinary concentrating ability, renal function, and renal morphology were assessed at adult age. The gene expression and localization of IGF-I, its receptor, and the growth hormone receptor (GHR) were investigated during ongoing ACE inhibition. The present study demonstrates normalized renal function and histology in enalapril + IGF-I-treated animals. Ongoing ACE inhibition suppressed the medullary IGF-I mRNA expression and altered the local distribution of both IGF-I and GHR. Thus the present study provides evidence for an interaction between the RAS and GH/IGF-I axis in renal development.
Oxytocin modulates the onset of murine parturition by competing ovarian and uterine effects
Authors: Imamura Takuji , Luedke Christina E. , Vogt Sherri K. , Muglia Louis J.
Published: December 2017

Recent analysis of mice deficient in both oxytocin (OT) and cyclooxygenase-1 has shown that OT exerts significant effects on both the ovarian corpus luteum and the uterine myometrium during pregnancy. To better define the roles of OT during pregnancy, we evaluated OT action and OT receptor regulation in wild-type and OT-deficient knockout (KO) mice. Continuous infusion of OT revealed that OT can either delay labor at low doses or initiate preterm labor at high doses. The infusion rates of OT necessary for these effects were reduced in OT KO mice. The dose of OT that delayed labor also delayed the normal decrease in plasma progesterone late in gestation, implicating a primary effect on the corpus luteum. Consistent with this hypothesis, luteal OT receptor expression exceeded that of the myometrium until luteolysis occurred. We propose that the downregulation of OT receptors in the corpus luteum and induction of OT receptors in the myometrium serve to shift the predominant consequence of OT action during murine pregnancy from labor inhibition to labor promotion.
Validity of V˙o 2 maxin predicting blood volume: implications for the effect of fitness on aging
Authors: Convertino Victor A. , Ludwig David A.
Published: December 2017

A multiple regression model was constructed to investigate the premise that blood volume (BV) could be predicted using several anthropometric variables, age, and maximal oxygen uptake (V˙o 2 max). To test this hypothesis, age, calculated body surface area (height/weight composite), percent body fat (hydrostatic weight), and V˙o 2 maxwere regressed on to BV using data obtained from 66 normal healthy men. Results from the evaluation of the full model indicated that the most parsimonious result was obtained when age andV˙o 2 max were regressed on BV expressed per kilogram body weight. The full model accounted for 52% of the total variance in BV per kilogram body weight. Both age andV˙o 2 max were related to BV in the positive direction. Percent body fat contributed <1% to the explained variance in BV when expressed in absolute BV (ml) or as BV per kilogram body weight. When the model was cross validated on 41 new subjects and BV per kilogram body weight was reexpressed as raw BV, the results indicated that the statistical model would be stable under cross validation (e.g., predictive applications) with an accuracy of ± 1,200 ml at 95% confidence. Our results support the hypothesis that BV is an increasing function of aerobic fitness and to a lesser extent the age of the subject. The results may have implication as to a mechanism by which aerobic fitness and activity may be protective against reduced BV associated with aging.
Functional characteristics of urinary tract smooth muscles in mice lacking cGMP protein kinase type I
Authors: Persson Katarina , Pandita Raj Kumar , Aszòdi Attila , Ahmad Marianne , Pfeifer Alexander , Fässler Reinhard , Andersson Karl-Erik
Published: December 2017

Nitric oxide (NO)-mediated smooth muscle relaxation is mediated by cGMP through activation of cGMP-dependent protein kinase I (cGKI). We studied the importance of cGKI for lower urinary tract function in mice lacking the gene for cGKI (cGKI−/−) and in litter-matched wild-type mice (cGKI+/+) in vitro and in vivo. cGKI deficiency did not result in any changes in bladder gross morphology or weight. Urethral strips from cGKI−/− mice showed an impaired relaxant response to nerve-derived NO. The cGMP analog 8-bromo-cGMP (8-BrcGMP) and the NO-donor SIN-1 relaxed the wild-type urethra (50–60%) but had only marginal effects in the cGKI-deficient urethra. Bladder strips from cGKI−/− mice responded normally to electrical field stimulation and to carbachol but not to 8-BrcGMP. In vivo, the cGKI-deficient mice showed bladder hyperactivity characterized by decreased intercontraction intervals and nonvoiding bladder contractions. Loss of cGKI abolishes NO-cGMP-dependent relaxations of urethral smooth muscle and results in hyperactive voiding. These data suggest that certain voiding disturbances may be associated with impaired NO-cGKI signaling.
Short photoperiods reduce vascular endothelial growth factor in the testes ofPeromyscus leucopus
Authors: Young Kelly A. , Nelson Randy J.
Published: December 2017

Testicular regression in rodents occurs after short-day exposure. Vascular support is withdrawn during regression, and, presumably, new angiogenesis is inhibited. Blood vessel growth and maintenance are regulated by paracrine factors, including vascular endothelial growth factor (VEGF). Reduced angiogenesis may contribute to the onset of photoperiod-induced regression; i.e., reduction of VEGF protein would be detected early during gonadal atrophy. Alternatively, loss of blood vessel maintenance may reflect reduced testicular volume. If true, VEGF would not be expected to decline until significant regression occurred. To discriminate between these hypotheses, white-footed mice ( Peromyscus leucopus) were maintained in either long (LD 16:8) or short (LD 8:16) photoperiod. Immunohistochemical and Western analyses revealed high VEGF expression in Leydig and Sertoli cells in long-day housed males and reduced VEGF expression in short-day housed males. Reductions in VEGF preceded decreases in both seminiferous tubule diameter and spermatogenic activity by 6 wk and reduced testis mass by 8 wk, suggesting that changes in VEGF are not a consequence of gonadal regression and that VEGF may play a critical role in photoperiodic regulation of testicular function.
Nonlinear response of the immune system to power-frequency magnetic fields
Authors: Marino Andrew A. , Wolcott R. Michael , Chervenak Robert , Jourd'Heuil Frances , Nilsen Erik , Frilot Clifton
Published: December 2017

Studies of the effects of power-frequency electromagnetic fields (EMFs) on the immune and other body systems produced positive and negative results, and this pattern was usually interpreted to indicate the absence of real effects. However, if the biological effects of EMFs were governed by nonlinear laws, deterministic responses to fields could occur that were both real and inconsistent, thereby leading to both types of results. The hypothesis of real inconsistent effects due to EMFs was tested by exposing mice to 1 G, 60 Hz for 1–105 days and observing the effect on 20 immune parameters, using flow cytometry and functional assays. The data were evaluated by means of a novel statistical procedure that avoided averaging away oppositely directed changes in different animals, which we perceived to be the problem in some of the earlier EMF studies. The reliability of the procedure was shown using appropriate controls. In three independent experiments involving exposure for 21 or more days, the field altered lymphoid phenotype even though the changes in individual immune parameters were inconsistent. When the data were evaluated using traditional linear statistical methods, no significant difference in any immune parameter was found. We were able to mimic the results by sampling from known chaotic systems, suggesting that deterministic chaos could explain the effect of fields on the immune system. We conclude that exposure to power-frequency fields produced changes in the immune system that were both real and inconsistent.
Interleukin-13 and transforming growth factor-β1 inhibit spontaneous sleep in rabbits
Authors: Kubota Takeshi , Fang Jidong , Kushikata Tetsuya , Krueger James M.
Published: December 2017

Proinflammatory cytokines, including interleukin-1β and tumor necrosis factor-α are involved in physiological sleep regulation. Interleukin (IL)-13 and transforming growth factor (TGF)-β1 are anti-inflammatory cytokines that inhibit proinflammatory cytokines by several mechanisms. Therefore, we hypothesized that IL-13 and TGF-β1 could attenuate sleep in rabbits. Three doses of IL-13 (8, 40, and 200 ng) and TGF-β1 (40, 100, and 200 ng) were injected intracerebroventricularly 3 h after the beginning of the light period. In addition, one dose of IL-13 (200 ng) and one dose of TGF-β1 (200 ng) were injected at dark onset. The two higher doses of IL-13 and the highest dose of TGF-β1 significantly inhibited spontanenous non-rapid eye movement sleep (NREMS) when they were given in the light period. IL-13 also inhibited NREMS after dark onset administration; however, the inhibitory effect was less potent than that observed after light period administration. The 40-ng dose of IL-13 inhibited REMS duration during the dark period. TGF-β1 administered at dark onset had no effect on sleep. These data provide additional evidence for the hypothesis that a brain cytokine network is involved in regulation of physiological sleep.
UTP binding and phosphoinositidase C activation in ampulla from frog semicircular canal
Authors: Teixeira Marie , Ferrary Evelyne , Butlen Daniel
Published: December 2017

Pyrimidine nucleotide-sensitive phosphoinositidase C activity (PLC), previously identified in frog semicircular canal ampulla, was pharmacologically characterized. Binding of [3H]UTP and abilities of unlabeled nucleotide analogs to inhibit binding and to stimulate PLC in myo-[3H]inositol-loaded ampullas were determined. Specific [3H]UTP binding was competitively inhibited by UTP [apparent dissociation binding constant = 0.8 μM; Hill coefficient = 0.7]. Scatchard analysis revealed a minor class of high-affinity binding sites [45 fmol UTP bound/μg protein; dissociation constant ( KD1) = 0.4 μM] and a major class of moderate-affinity binding sites (365 fmol UTP bound/μg protein; KD2= 10 μM). The stereospecificity pattern for UTP analog recognition was UMP > UDP ≥ ADP = UTP = dTTP > adenosine 5′- O-(3-thiotriphosphate) = ATP = CTP = 2′-and 3′- O-4-(benzoylbenzoyl)-ATP (Bz-ATP) ≥ AMP ≥ 2-methylthio-ATP = α,β-methylene-ATP > uridine = diadenosine tetraphosphate (Ap4A); cAMP and adenosine were inactive. Antagonist recognition pattern was DIDS = pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) = reactive blue 2 > suramin. The rank order of potencies for agonist-induced PLC activation was UDP ≥ UTP ≥ Ap4A ≥ UMP = Bz-ATP; uridine was inactive. UTP-stimulated PLC activity was inhibited by DIDS = reactive blue 2 = PPADS > suramin. These results suggest that the population of [3H]UTP-labeled binding sites is heterogeneous, with a low number of high-affinity UTP receptors whose function(s) need to be determined and a large number of moderate-affinity receptors triggering PLC activation.
Low LBNP tolerance in men is associated with attenuated activation of the renin-angiotensin system
Authors: Greenleaf John E. , Petersen Trine Welløw , Gabrielsen Anders , Pump Bettina , Bie Peter , Christensen Niels Juel , Warberg Jørgen , Videbaek Regitze , Simonson Shawn R. , Norsk Peter
Published: December 2017

Plasma vasoactive hormone concentrations [epinephrine (pEpi), norepinephrine (pNE), ANG II (pANG II), vasopressin (pVP), endothelin-1 (pET-1)] and plasma renin activity (pRA) were measured periodically and compared during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the renin-angiotensin system, the latter being one of the most powerful vasoconstrictors in the body, is of major importance for LBNP tolerance. Healthy men on a controlled diet (2,822 cal/day, 2 mmol · kg−1· day−1 Na+) were exposed to 30 min of LBNP from −15 to −50 mmHg. LBNP was uneventful for seven men [25 ± 2 yr, high-tolerance (HiTol) group], but eight men (26 ± 3 yr) reached presyncope after 11 ± 1 min [ P < 0.001, low-tolerance (LoTol) group]. Mean arterial pressure (MAP) did not change measurably, but central venous pressure and left atrial diameter decreased similarly in both groups (5–6 mmHg, by ≈30%, P < 0.05). Control (0 mmHg LBNP) hormone concentrations were similar between groups, however, pRAdiffered between them (LoTol 0.6 ± 0.1, HiTol 1.2 ± 0.1 ng ANG I · ml−1 · h−1, P < 0.05). LBNP increased ( P < 0.05) pRA and pANG II, respectively, more in the HiTol group (9.9 ± 2.2 ng ANG I · ml−1· h−1 and 58 ± 12 pg/ml) than in LoTol subjects (4.3 ± 0.9 ng ANG I · ml−1 · h−1 and 28 ± 6 pg/ml). In contrast, the increase in pVP was higher ( P < 0.05) in the LoTol than in the HiTol group. The increases ( P < 0.05) for pNE were nonsignificant between groups, and pET-1 remained unchanged. Thus there may be a causal relationship between attenuated activation of pRA and pANG II and presyncope, with pVP being a possible cofactor. Measurement of resting pRA may be of predictive value for those with lower hypotensive tolerance.
Afferent pathways in cardiovascular adjustments induced by volume expansion in anesthetized rats
Authors: Colombari Débora S. A. , Colombari Eduardo , Lopes Oswaldo U. , Cravo Sérgio L.
Published: December 2017

The role of baroreceptors, cardiopulmonary receptors, and renal nerves in the cardiovascular adjustments to volume expansion (VE) with 4% Ficoll (Pharmacia; 1% body wt, 0.4 ml/min) were studied in urethan-anesthetized rats. In control animals, VE produced a transitory increase in mean arterial pressure (MAP), which peaked at 10 min (17 ± 4 mmHg) and increases in renal (128 ± 6 and 169 ± 19% of baseline at 10 and 40 min, respectively) and hindlimb vascular conductance (143 ± 6 and 150 ± 10%). These cardiovascular adjustments to VE were unaffected by bilateral vagotomy. After sinoaortic denervation, the increase in MAP induced by VE was greater than in control rats (30 ± 4 mmHg). However, renal vasodilation in response to VE was blocked, whereas hindlimb vasodilation was similar to that observed in control rats. After unilateral renal denervation (ipsilateral to flow recording), the initial renal vasodilation was blocked. However, 40 min after VE, a significant renal vasodilation (125 ± 4%) appeared. The hindlimb vasodilation and MAP responses were unaffected by renal denervation. These results demonstrate that the baroreceptor afferents are an essential component of cardiovascular adjustments to VE, especially in the control of renal vascular conductance. They also suggest that renal vasodilation induced by VE is mediated by neural and hormonal mechanisms.
Differential neural control of intrarenal blood flow
Authors: Leonard Bridget L. , Evans Roger G. , Navakatikyan Michael A. , Malpas Simon C.
Published: December 2017

To test whether renal sympathetic nerve activity (RSNA) can differentially regulate blood flow in the renal medulla (MBF) and cortex (CBF) of pentobarbital sodium-anesthetized rabbits, we electrically stimulated the renal nerves while recording total renal blood flow (RBF), CBF, and MBF. Three stimulation sequences were applied 1) varying amplitude (0.5–8 V), 2) varying frequency (0.5–8 Hz), and 3) a modulated sinusoidal pattern of varying frequency (0.04–0.72 Hz). Increasing amplitude or frequency of stimulation progressively decreased all flow variables. RBF and CBF responded similarly, but MBF responded less. For example, 0.5-V stimulation decreased CBF by 20 ± 9%, but MBF fell by only 4 ± 6%. The amplitude of oscillations in all flow variables was progressively reduced as the frequency of sinusoidal stimulation was increased. An increased amplitude of oscillation was observed at 0.12 and 0.32 Hz in MBF and to a lesser extent RBF, but not CBF. MBF therefore appears to be less sensitive than CBF to the magnitude of RSNA, but it is more able to respond to these higher frequencies of neural stimulation.
Activation of cardiorenal and pulmonary tissue endothelin-1 in experimental heart failure
Authors: Luchner A. , Jougasaki M. , Friedrich E. , Borgeson D. D. , Stevens T. L. , Redfield M. M. , Riegger G. A. J. , Burnett J. C.
Published: December 2017

Endothelin-1 (ET-1) is a peptide that has been implicated in congestive heart failure (CHF). Although increased concentrations of circulating ET-1 have been repeatedly demonstrated, the activation of local ET-1 in target tissues of CHF remains poorly defined. Our objective was to characterize ET-1 tissue concentrations and gene expression of prepro ET-1 in myocardial, renal, and pulmonary tissue in rapid ventricular pacing-induced canine CHF. Progressive rapid ventricular pacing (38 days) resulted in impaired cardiovascular hemodynamics, increased atrial and left ventricular mass, decreased renal sodium excretion, and increased ET-1 plasma concentrations (all P < 0.05). Tissue analysis revealed significant increases in local ET-1 during CHF in left ventricular, renal, and pulmonary tissue, whereas a moderate increase in left atrial ET-1 did not reach statistical significance. In contrast, prepro-ET-1 gene expression was increased more than threefold in pulmonary tissue and more than twofold in left atrial myocardium with no increase in left ventricular or renal gene expression. The present studies demonstrate a differential pattern of ET-1 activation in cardiorenal and pulmonary tissue with a strong accumulation of ET-1 in kidney and lung during CHF. Although the observed increase in left ventricular and renal ET-1 in association with unaltered gene expression is consistent with increased uptake, pulmonary and atrial tissue may contribute to increased circulating and local ET-1 in CHF.
Mobilization of NK cells by exercise: downmodulation of adhesion molecules on NK cells by catecholamines
Authors: Nagao Fumiko , Suzui Masatoshi , Takeda Kazuyoshi , Yagita Hideo , Okumura Ko
Published: December 2017

The change of plasma catecholamine concentration correlates with the change of natural killer (NK) activity and NK cell number in peripheral blood mononuclear cells (PBMC) during and after moderate exercise. We studied the causal relation between exercise-induced catecholamine and expression of adhesion molecules on NK cells during and after exercise. The expression of CD44 and CD18 on CD3−CD56+NK cells was significantly reduced during exercise ( P < 0.01). When PBMC were stimulated with 10−8M norepinephrine in vitro, the expression of these adhesion molecules on CD3−CD56+NK cells was downmodulated within 30 min. The binding capacity of NK cells to a CD44 ligand, hyaluronate, was reduced by the stimulation with norepinephrine ( P< 0.01). The intravenous injection of norepinephrine in mice decreased the expression of CD44 and CD18 on CD3−NK1.1+cells ( P < 0.01) and increased the number of CD3−NK1.1+cells in PBMC ( P < 0.01). These findings suggest that exercise-induced catecholamines modulate the expression of adhesion molecules on NK cells, resulting in the mobilization of NK cells into the circulation.
Treadmill running produces both positive and negative physiological adaptations in Sprague-Dawley rats
Authors: Moraska Albert , Deak Terrence , Spencer Robert L. , Roth David , Fleshner Monika
Published: December 2017

Exercise training produces a vast array of physiological adaptations, ranging from changes in metabolism to muscle mitochondrial biogenesis. Researchers studying the physiological effects of exercise often use animal models that employ forced exercise regimens that include aversive motivation, which could activate the stress response. This study examined the effect of forced treadmill running (8 wk) on several physiological systems that are sensitive to training and stress. Forced treadmill running produced both positive and negative physiological adaptations. Indicative of positive training adaptations, exercised male Sprague-Dawley rats had a decrease in body weight gain and an increase in muscle citrate synthase activity compared with sedentary controls. In contrast, treadmill running also resulted in the potentially negative adaptations of adrenal hypertrophy, thymic involution, decreased serum corticosteroid binding globulin, elevated lymphocyte nitrite concentrations, suppressed lymphocyte proliferation, and suppressed antigen-specific IgM. Such alterations in neuroendocrine tissues and immune responses are commonly associated with chronic stress. Thus treadmill running produces both positive training adaptations and potentially negative adaptations that are indicative of chronic stress. Researchers employing forced activity need to be aware that this type of exercise procedure also produces physiological adaptations indicative of chronic stress and that these changes could potentially impact other measures of interest.
Osteoblast tissue-nonspecific alkaline phosphatase antagonizes and regulates PC-1
Authors: Johnson K. A. , Hessle L. , Vaingankar S. , Wennberg C. , Mauro S. , Narisawa S. , Goding J. W. , Sano K. , Millan J. L. , Terkeltaub R.
Published: December 2017

Tissue-nonspecific alkaline phosphatase (TNAP) is essential for bone matrix mineralization, but the central mechanism for TNAP action remains undefined. We observed that ATP-dependent45Ca precipitation was decreased in calvarial osteoblast matrix vesicle (MV) fractions from TNAP−/− mice, a model of infantile hypophosphatasia. Because TNAP hydrolyzes the mineralization inhibitor inorganic pyrophosphate (PPi), we assessed phosphodiesterase nucleotide pyrophosphatase (PDNP/NTPPPH) activity, which hydrolyzes ATP to generate PPi. Plasma cell membrane glycoprotein-1 (PC-1), but not the isozyme B10 (also called PDNP3) colocalized with TNAP in osteoblast MV fractions and pericellular matrix. PC-1 but not B10 increased MV fraction PPiand inhibited45Ca precipitation by MVs. TNAP directly antagonized inhibition by PC-1 of MV-mediated45Ca precipitation. Furthermore, the PPicontent of MV fractions was greater in cultured TNAP−/− than TNAP+/+ calvarial osteoblasts. Paradoxically, transfection with wild-type TNAP significantly increased osteoblast MV fraction NTPPPH. Specific activity of NTPPPH also was twofold greater in MV fractions of osteoblasts from TNAP+/+ mice relative to TNAP−/− mice. Thus TNAP attenuates PC-1/NTPPPH-induced PPigeneration that would otherwise inhibit MV-mediated mineralization. TNAP also paradoxically regulates PC-1 expression and NTPPPH activity in osteoblasts.
Does angiotensin II have a significant tonic action on cardiovascular neurons in the rostral and caudal VLM?
Authors: Potts P. D. , Allen A. M. , Horiuchi J. , Dampney R. A. L.
Published: December 2017

The peptidic ANG II receptor antagonists [Sar1,Ile8]ANG II (sarile) or [Sar1,Thr8]ANG II (sarthran) are known to decrease arterial pressure and sympathetic activity when injected into the rostral part of the ventrolateral medulla (VLM). In anesthetized rabbits and rats, the profound depressor and sympathoinhibitory response after bilateral microinjections of sarile or sarthran into the rostral VLM was unchanged after prior selective blockade of angiotensin type 1 (AT1) and ANG-(1—7) receptors, although this abolished the effects of exogenous ANG II. Unlike the neuroinhibitory compounds muscimol or lignocaine, microinjections of sarile in the rostral VLM did not affect respiratory activity. Sarile or sarthran in the caudal VLM resulted in a large pressor and sympathoexcitatory response, which was also unaffected by prior blockade of AT1and ANG-(1—7) receptors. The results indicate that the peptidic ANG receptor antagonists profoundly inhibit the tonic activity of cardiovascular but not respiratory neurons in the VLM and that these effects are independent of ANG II or ANG-(1—7) receptors.