bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise training enhances baroreflex control of heart rate by a vagal mechanism in rabbits with heart failure
Authors: Liu Jun-Li , Kulakofsky Jay , Zucker Irving H.
Published: March 2015

Moderate exercise training (Ex) enhances work capacity and quality of life in patients with chronic heart failure (CHF). We investigated the autonomic components of resting heart rate (HR) and the baroreflex control of HR in conscious, instrumented rabbits with pacing-induced CHF after Ex. Sham and CHF rabbits were exercise trained for 4 wk at 15–18 m/min, 6 days/wk. Arterial pressure and HR were recorded before and after metoprolol (1 mg/kg iv) or after atropine (0.2 mg/kg iv). Mean arterial pressure was altered by infusions of sodium nitroprusside and phenylephrine. The data were fit to a sigmoid (logistic) function. Baseline HRs were 266.5 ± 8.4 and 232.1 ± 1.6 beats/min in CHF and CHF Ex rabbits, respectively ( P < 0.05). In the unblocked state, CHF rabbits had a significantly depressed peak baroreflex slope (1.7 ± 0.3 vs. 5.6 ± 0.7 beats · min−1 · mmHg−1; P < 0.001) and HR range (128.6 ± 34.5 vs. 253.2 ± 20.3 beats/min; P < 0.05) compared with normal subjects. Ex increased baroreflex slope to 4.9 ± 0.3 from 1.7 ± 0.3 beats · min−1 · mmHg−1 in unblocked rabbits ( P < 0.001 compared with CHF non-Ex). Ex did not alter baroreflex function in sham animals. After metoprolol, baroreflex slope was significantly increased in CHF Ex rabbits (1.5 ± 0.2 vs. 3.0 ± 0.2 beats · min−1 · mmHg−1; P < 0.05). After atropine, there was no significant change in baroreflex slope or HR range between CHF Ex and CHF rabbits. These data support the view that enhancement of baroreflex control of HR after Ex is due to an augmentation of vagal tone.
The human spleen as an erythrocyte reservoir in diving-related interventions
Authors: Espersen Kurt , Frandsen Hans , Lorentzen Torben , Kanstrup Inge-Lis , Christensen Niels J.
Published: March 2015

Twelve subjects without and ten subjects with diving experience performed short diving-related interventions. After labeling of erythrocytes, scintigraphic measurements were continuously performed during these interventions. All interventions elicited a graduated and reproducible splenic contraction, depending on the type, severity, and duration of the interventions. The splenic contraction varied between ∼10% for “apnea” (breath holding for 30 s) and “cold clothes” (cold and wet clothes applied on the face with no breath holding for 30 s) and ∼30–40% for “simulated diving” (simulated breath-hold diving for 30 s), “maximal apnea” (breath holding for maximal duration), and “maximal simulated diving” (simulated breath-hold diving for maximal duration). The strongest interventions (simulated diving, maximal apnea, and maximal simulated diving) elicited modest but significant increases in hemoglobin concentration (0.1–0.3 mmol/l) and hematocrit (0.3–1%). By an indirect method, the splenic venous hematocrit was calculated to 79%. No major differences were observed between the two groups. The splenic contraction should, therefore, be included in the diving response on equal terms with bradycardia, decreased peripheral blood flow, and increased blood pressure.
Human skeletal muscle responses vary with age and gender during fatigue due to incremental isometric exercise
Authors: Kent-Braun J. A. , Ng A. V. , Doyle J. W. , Towse T. F.
Published: March 2015

The purpose of this study was to compare the magnitude and mechanisms of ankle dorsiflexor muscle fatigue in 20 young (33 ± 6 yr, mean ± SD) and 21 older (75 ± 6 yr) healthy men and women of similar physical activity status. Noninvasive measures of central and peripheral (neuromuscular junction, sarcolemma) muscle activation, muscle contractile function, and intramuscular energy metabolism were made before, during, and after incremental isometric exercise. Older subjects fatigued less than young ( P < 0.01); there was no effect of gender on fatigue ( P = 0.24). For all subjects combined, fatigue was modestly related to preexercise strength ( r = 0.49, P < 0.01). Neither central (central activation ratio) nor peripheral (compound muscle action potential) activation played a significant role in fatigue in any group. During exercise, intracellular concentrations of Piand H2PO[Formula: see text] increased more and pH fell more in young compared with older subjects ( P < 0.01) and in men compared with women ( P < 0.01). These varied metabolic responses to exercise suggest a greater reliance on nonoxidative sources of ATP in young compared with older subjects and in men compared with women. These results suggest that the mechanisms of fatigue vary with age and gender, regardless of whether differences in the magnitude of fatigue are observed.
Breath [13CO2] recovery from an oral glucose load during exercise: comparison between [U-13C] and [1,2-13C]glucose
Authors: Ruzzin J. , Péronnet F. , Tremblay J. , Massicotte D. , Lavoie C.
Published: March 2015

The purpose of the present experiment was to compare 13CO2 recovery at the mouth, and the corresponding exogenous glucose oxidation computed, during a 100-min exercise at 63 ± 3% maximal O2 uptake with ingestion of glucose (1.75 g/kg) in six active male subjects, by use of [U-13C] and [1,2-13C]glucose. We hypothesized that 13C recovery and exogenous glucose oxidation could be lower with [1,2-13C] than [U-13C]glucose because both tracers provide [13C]acetate, with possible loss of 13C in the tricarboxylic acid (TCA) cycle, but decarboxylation of pyruvate from [U-13C]glucose also provides 13CO2, which is entirely recovered at the mouth during exercise. The recovery of 13C (25.8 ± 2.3 and 27.4 ± 1.2% over the exercise period) and the amounts of exogenous glucose oxidized computed were not significantly different with [1,2-13C] and [U-13C]glucose (28.9 ± 2.6 and 30.7 ± 1.3 g, between minutes 40 and 100), suggesting that no significant loss of 13C occurred in the TCA cycle. This stems from the fact that, during exercise, the rate of exogenous glucose oxidation is probably much larger than the flux of the metabolic pathways fueled from TCA cycle intermediates. It is thus unlikely that a significant portion of the 13C entering the TCA cycle could be diverted to these pathways. From a methodological standpoint, this result indicates that when a large amount of [13C]glucose is ingested and oxidized during exercise, 13CO2 production at the mouth accurately reflects the rate of glucose entry in the TCA cycle and that no correction factor is needed to compute the oxidative flux of exogenous glucose.
Acute and chronic effects of exercise on tissue sensitivity to glucocorticoids
Authors: Duclos M. , Gouarne C. , Bonnemaison D.
Published: March 2015

The aim of this study was to address the effect of endurance training on tissue sensitivity to glucocorticoids (GC) in both resting and exercising conditions. In vitro dexamethasone inhibition of LPS-induced interleukin-6 secretion in cultures of peripheral monocytes was compared in untrained subjects (UT) and in endurance-trained men (ET) at the end of a 2-h run and during exercise recovery. We demonstrated an in vitro plasticity of sensitivity of monocytes to GC in ET men, superimposed to changes in systemic cortisol concentrations (plasma and saliva). Compared with sedentary men, similar resting cortisol levels in ET men are associated with decreased sensitivity of monocytes to GC 8 and 24 h after the end of the last training session ( P < 0.05, ET vs. UT). Moreover, in these ET subjects, an acute bout of exercise increased the sensitivity of monocytes to GC (at 1000 and 1200; ET vs. UT, P > 0.05). This acute exercise-induced increase in tissue sensitivity to GC, which is synchronous with activation of the hypothalamo-pituitary adrenal axis, may act to shut off muscle inflammatory reaction and cytokine synthesis and then decrease exercise-induced muscle damage or inflammatory response. By contrast, the decreased sensitivity of monocytes to GC reported in ET men 24 h after the last bout of exercise may be related to the process of desensitization that may act to protect the body from prolonged, exercise-induced cortisol secretion. These acute and chronic effects of exercise on tissue sensitivity to GC demonstrate an adaptation of the hypothalamo-pituitary adrenal axis to repeated and prolonged exercise-induced increases in GC secretion.
Metabolic costs induced by lactate in the toadBufo marinus: new mechanism behind oxygen debt?
Authors: Pinz Ilka , Pörtner Hans-O.
Published: March 2015

The mechanism of an increase in metabolic rate induced by lactate was investigated in the toad Bufo marinus. Oxygen consumption (V˙o2) was analyzed in fully aerobic animals under hypoxic conditions (7% O2in air), accompanied by measurements of catecholamines in the plasma, and was measured in isolated hepatocytes in vitro under normoxia by using specific inhibitors of lactate proton symport [α-cyano-4-hydroxycinnamate (CHC)] and sodium proton exchange (EIPA). The rise in metabolic rate in vivo can be elicited by infusions of hyperosmotic (previous findings) or isosmotic sodium lactate solutions (this study). Despite previous findings of reduced metabolic stimulation under the effect of adrenergic blockers, the increase inV˙o2in vivo was not associated with elevated plasma catecholamine levels, suggesting local release and effect. In addition to the possible in vivo effect via catecholamines, lactate induced a rise in V˙o2of isolated hepatocytes, depending on the concentration present in a weakly buffered Ringer solution at pH 7.0. No increase was found at higher pH values (7.4 or 7.8) or in HEPES-buffered Ringer solution. Inhibition of the Lac−-H+transporter with α-CHC or of the Na+/H+exchanger with EIPA prevented the increase in metabolic rate. We conclude that increasedV˙o2at an elevated systemic lactate level may involve catecholamine action, but it is also caused by an increased energy demand of cellular acid-base regulation via stimulation of Na+/H+exchange and thereby Na+-K+-ATPase. The effect depends on entry of lactic acid into the cells via lactate proton symport, which is likely favored by low cellular surface pH. We suggest that these energetic costs should also be considered in other physiological phenomena, e.g., when lactate is present during excess, postexerciseV˙o2.
Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs
Authors: Turner Debra J. , Noble Peter B. , Lucas Matthew P. , Mitchell Howard W.
Published: March 2015

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0–20 cmH2O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls ( P < 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi ( P < 0.01) and smooth muscle strips ( P < 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs.
Effects of body posture and tidal volume on inter- and intraregional ventilation distribution in healthy men
Authors: Grönkvist Mikael , Bergsten Eddie , Gustafsson Per M.
Published: March 2015

The influences of body posture and tidal volume (Vt) on inter- and intraregional ventilation inhomogeneity were assessed by normalized phase III slope ( SnIII) analysis of multiple-breath washout recordings of SF6 and He in 11 healthy men. Washouts with target Vt of 750, 1,000, and 1,250 ml were performed standing and supine. A linear-fit method was used to establish the contributions of convection-dependent (interregional) (cdi) and diffusion-convection interaction-dependent (intraregional) inhomogeneity (dcdi). Overall inhomogeneity was defined as the sum of cdi and dcdi. The difference in first-breath SnIII for SF6 vs. He, the (SF6 − He) SnIII, served as an index of intra-acinar inhomogeneity. Multiple-regression analysis revealed greater cdi supine vs. standing ( P < 0.001) but no significant effects of posture on dcdi or overall inhomogeneity. Larger Vt were associated with greater cdi ( P < 0.001), particularly when supine, but reduced dcdi ( P < 0.001), overall inhomogeneity ( P < 0.001), and (SF6 − He) SnIII ( P = 0.031). In conclusion, during resting breathing overall and intraregional ventilation inhomogeneities remain unchanged when the supine posture is assumed and improve with larger Vt, but supine posture and larger breaths result in greater interregional inhomogeneities.
Male and female rats express similar blood pressure responses to “push-pull” gravitational stress
Authors: Hakeman Amy L. , Sheriff Don D.
Published: March 2015

Brief exposure to −Gz (“push”) reduces eye-level blood pressure (elbp) during subsequent exposure to +Gz(“pull”). This is called the “push-pull effect.” To evaluate the influence of gender and the axis of rotation (pitch vs. roll) on the push-pull effect, 10 isoflurane-anesthetized male and 10 female Sprague-Dawley rats were restrained supine on a heated tilt board. Rats were subjected to two G profiles: a control profile consisting of rotation from 0 Gz to 90° head-up tilt (+1 Gz) for 10 s and a push-pull profile consisting of rotation from 0 Gz to 90° head-down tilt (−1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. A total of 16 tilts consisting of equal numbers of control and push-pull trials and equal numbers of pitch and roll rotations were imposed by using a counterbalanced design. Gender exerted a significant effect on baseline (0 Gz) ELBP (pressure was ∼4 mmHg higher in females). In males and females, ELBP rose to a similar extent (∼8 mmHg) during push, fell to a similar extent (∼18 mmHg) during control +Gz stress, and fell to a similar extent (∼22 mmHg) during push-pull +Gz stress. Altering the axis of rotation between the x-axis (roll) and the y-axis (pitch) did not influence the results. Thus males and females exhibit a push-pull effect; however, gender and axis of rotation do not appear to influence the push-pull effect in anesthetized rats subjected to tilting.
ATP concentrations and muscle tension increase linearly with muscle contraction
Authors: Li Jianhua , King Nicholas C. , Sinoway Lawrence I.
Published: March 2015

Previous studies have suggested that activation of ATP-sensitive P2X receptors in skeletal muscle play a role in mediating the exercise pressor reflex (Li J and Sinoway LI. Am J Physiol Heart Circ Physiol 283: H2636–H2643, 2002). To determine the role ATP plays in this reflex, it is necessary to examine whether muscle interstitial ATP (ATPi) concentrations rise with muscle contraction. Accordingly, in this study, muscle contraction was evoked by electrical stimulation of the L7and S1ventral roots of the spinal cord in 12 decerebrate cats. Muscle ATPiwas collected from microdialysis probes inserted in the muscle. ATP concentrations were determined by the HPLC method. Electrical stimulation of the ventral roots at 3 and 5 Hz increased mean arterial pressure by 13 ± 2 and 16 ± 3 mmHg ( P < 0.05), respectively, and it increased ATP concentration in contracting muscle by 150% ( P < 0.05) and 200% ( P < 0.05), respectively. ATP measured in the opposite control limb did not rise with ventral root stimulation. Section of the L7and S1dorsal roots did not affect the ATPiseen with 5-Hz ventral root stimulation. Finally, ventral roots stimulation sufficient to drive motor nerve fibers did not increase ATP in previously paralyzed cats. Thus ATPiis not largely released from sympathetic or motor nerves and does not require an intact afferent reflex pathway. We conclude that ATPiis due to the release of ATP from contracting skeletal muscle cells.
Invited Review: Aging and human temperature regulation
Authors: Kenney W. Larry , Munce Thayne A.
Published: March 2015

This mini-review focuses on the effects of aging on human temperature regulation. Although comprehensive reviews have been published on this topic (Kenney WL. Exercise and Sport Sciences Reviews, Baltimore: Williams & Wilkins, 1997, p. 41-76; Pandolf KB. Exp Aging Res 17: 189-204, 1991; Van Someren EJ, Raymann RJ, Scherder EJ, Daanen HA, and Swaab DF. Ageing Res Rev 1: 721-778, 2002; and Young AJ. Exp Aging Res 17: 205-213, 1991), this mini-review concisely summarizes the present state of knowledge about human temperature regulation and aging in thermoneutral conditions, as well as during hypo- and hyperthermic challenges. First, we discuss age-related effects on baseline body core temperature and phasing rhythms of the circadian temperature cycle. We then examine the altered physiological responses to cold stress that result from aging, including attenuated peripheral vasoconstriction and reduced cold-induced metabolic heat production. Finally, we present the age-related changes in sweating and cardiovascular function associated with heat stress. Although epidemiological evidence of increased mortality among older adults from hypo- and hyperthermia exists, this outcome does not reflect an inability to thermoregulate with advanced age. In fact, studies that have attempted to separate the effects of chronological age from concurrent factors, such as fitness level, body composition, and the effects of chronic disease, have shown that thermal tolerance appears to be minimally compromised by age.
Ventilatory response to exercise in aged runners breathing He-O2 or inspired CO2
Authors: Babb T. G. , DeLorey Darren S. , Wyrick Brenda L.
Published: March 2015

The ventilatory response to exercise below ventilatory threshold (VTh) increases with aging, whereas above VTh the ventilatory response declines only slightly. We wondered whether this same ventilatory response would be observed in older runners. We also wondered whether their ventilatory response to exercise while breathing He-O2 or inspired CO2would be different. To investigate, we studied 12 seniors (63 ± 4 yr; 10 men, 2 women) who exercised regularly (5 ± 1 days/wk, 29 ± 11 mi/wk, 16 ± 6 yr). Each subject performed graded cycle ergometry to exhaustion on 3 separate days, breathing either room air, 3% inspired CO2, or a heliox mixture (79% He and 21% O2). The ventilatory response to exercise below VTh was 0.35 ± 0.06 l · min−1 · W−1and above VTh was 0.66 ± 0.10 l · min−1 · W−1. He-O2 breathing increased ( P < 0.05) the ventilatory response to exercise both below (0.40 ± 0.12 l · min−1 · W−1) and above VTh (0.81 ± 0.10 l · min−1 · W−1). Inspired CO2 increased ( P < 0.001) the ventilatory response to exercise only below VTh (0.44 ± 0.10 l · min−1 · W−1). The ventilatory responses to exercise with room air, He-O2, and CO2 breathing of these fit runners were similar to those observed earlier in older sedentary individuals. These data suggest that the ventilatory response to exercise of these senior runners is adequate to support their greater exercise capacity and that exercise training does not alter the ventilatory response to exercise with He-O2 or inspired CO2 breathing.
Spleen volume and blood flow response to repeated breath-hold apneas
Authors: Baković Darija , Valic Zoran , Eterović Davor , Vuković Ivica , Obad Ante , Marinović-Terzić Ivana , Dujić Z̆eljko
Published: March 2015

The purpose of this study was 1) to answer whether the reduction in spleen size in breath-hold apnea is an active contraction or a passive collapse secondary to reduced splenic arterial blood flow and 2) to monitor the spleen response to repeated breath-hold apneas. Ten trained apnea divers and 10 intact and 7 splenectomized untrained persons repeated five maximal apneas (A1-A5) with face immersion in cold water, with 2 min interposed between successive attempts. Ultrasonic monitoring of the spleen and noninvasive cardiopulmonary measurements were performed before, between apneas, and at times 0, 10, 20, 40, and 60 min after the last apnea. Blood flows in splenic artery and splenic vein were not significantly affected by breath-hold apnea. The duration of apneas peaked after A3 (143, 127, and 74 s in apnea divers, intact, and splenectomized persons, respectively). A rapid decrease in spleen volume (∼20% in both apnea divers and intact persons) was mainly completed throughout the first apnea. The spleen did not recover in size between apneas and only partly recovered 60 min after A5. The well-known physiological responses to apnea diving, i.e., bradycardia and increased blood pressure, were observed in A1 and remained unchanged throughout the following apneas. These results show rapid, probably active contraction of the spleen in response to breath-hold apnea in humans. Rapid spleen contraction and its slow recovery may contribute to prolongation of successive, briefly repeated apnea attempts.
Peripheral cholinergic pathway modulates hyperthermia induced by stress in rats exposed to open-field stress
Authors: Rowsey Pamela Johnson , Yang Yong-Lu , Gordon Christopher J.
Published: March 2015

Exposure to an open field is psychologically stressful and leads to an elevation in core temperature (Tc). Methyl scopolamine (MS), a muscarinic antagonist, and pyridostigmine (PYR), a carbamate that inhibits acetylcholinesterase, do not cross the blood-brain barrier and have little effect on Tc in resting, nonstressed animals. However, we have found that MS has an antipyretic effect on Tc that is caused by handling and cage-switch stress. PYR should act pharmacologically to reverse the effects of MS. To this end, we assessed the effects of MS and PYR on stress-induced hyperthermia. Male Sprague-Dawley rats at 90 days of age were housed individually at an ambient temperature of 22°C. Tc and motor activity were monitored by radiotelemetry in an open-field chamber. Rats were dosed intraperitoneally at 1200 with 1.0 mg/kg MS, 0.1 mg/kg PYR, a combination of MS and PYR, or saline and placed immediately inside the open-field chamber for 60 min. Stress-induced hyperthermia was suppressed immediately by MS and enhanced by PYR. Tc only increased by 0.3°C in the MS-treated animals. The hyperthermic response in the PYR group was nearly 0.6°C above that of rats dosed with saline. Coadministration of PYR and MS led to a stress-induced hyperthermia response nearly identical to that of rats injected with saline. Overall, open-field stress exacerbated the effects of MS and PYR on body Tc and provides support for a peripheral cholinergic mechanism that mediates stress-induced hyperthermia.
Neurohumoral responses during prolonged exercise in humans
Authors: Nybo Lars , Nielsen Bodil , Blomstrand Eva , Møller Kirsten , Secher Niels
Published: March 2015

This study examined neurohumoral alterations during prolonged exercise with and without hyperthermia. The cerebral oxygen-to-carbohydrate uptake ratio (O2/CHO = arteriovenous oxygen difference divided by arteriovenous glucose difference plus one-half lactate), the cerebral balances of dopamine, and the metabolic precursor of serotonin, tryptophan, were evaluated in eight endurance-trained subjects during exercise randomized to be with or without hyperthermia. The core temperature stabilized at 37.9 ± 0.1°C (mean ± SE) in the control trial, whereas it increased to 39.7 ± 0.2°C in the hyperthermic trial, with a concomitant increase in perceived exertion ( P < 0.05). At rest, the brain had a small release of tryptophan (arteriovenous difference of -1.2 ± 0.3 μmol/l), whereas a net balance was obtained during the two exercise trials. Both the arterial and jugular venous dopamine levels became elevated during the hyperthermic trial, but the net release from the brain was unchanged. During exercise, the O2/CHO was similar across trials, but, during recovery from the hyperthermic trial, the ratio decreased to 3.8 ± 0.3 ( P < 0.05), whereas it returned to the baseline level of ∼6 within 5 min after the control trial. The lowering of O2/CHO was established by an increased arteriovenous glucose difference (1.1 ± 0.1 mmol/l during recovery from hyperthermia vs. 0.7 ± 0.1 mmol/l in control; P < 0.05). The present findings indicate that the brain has an increased need for carbohydrates during recovery from strenuous exercise, whereas enhanced perception of effort as observed during exercise with hyperthermia was not related to alterations in the cerebral balances of dopamine or tryptophan.
Evidence for sympatholysis at the onset of forearm exercise
Authors: DeLorey Darren S. , Wang Simon S. , Shoemaker J. Kevin
Published: March 2015

The effect of augmented sympathetic outflow on forearm vascular conductance after single handgrip contractions of graded intensity was examined to determine whether sympatholysis occurs early in exercise ( n = 7). While supine, subjects performed contractions that were 1 s in duration and 15, 30, and 60% of maximal voluntary contraction (MVC) in intensity. The contractions were repeated during control and lower body negative pressure (LBNP) (−40 mmHg) sessions. Forearm blood flow (FBF; Doppler ultrasound) and mean arterial pressure were measured continuously for 30 s before and 60 s after the single contractions. Vascular conductance (VC) was calculated. Total postcontraction blood flow increased in an exercise intensity-dependent manner. Compared with control, LBNP caused a reduction in baseline and postexercise FBF ( P < 0.05), VC ( P < 0.01), as well as total excess flow ( P < 0.01). Specifically, during LBNP, baseline FBF and VC were reduced by 29 and 34% of control, respectively ( P < 0.05). After the 15% MVC contraction, peak VC during LBNP was reduced by a magnitude similar to that during baseline (i.e., ∼30%), but it was only reduced by 15% during both the 30 and 60% MVC trials ( P < 0.01). It was concluded that the stimuli for exercise hyperemia during moderate and heavy, but not mild, handgrip exercise intensities, diminish the vasoconstrictor effects of LBNP. Furthermore, these data demonstrate that this sympatholysis occurs early in exercise.
Nitric oxide contributes to 20-HETE-induced relaxation of pulmonary arteries
Authors: Yu Ming , McAndrew Ryan P. , Al-Saghir Rula , Maier Kristopher G. , Medhora Meetha , Roman Richard J. , Jacobs Elizabeth R.
Published: March 2015

In contrast to its constrictor effects on peripheral arteries, 20-hydroxyeicosatetraenoic acid (20-HETE) is an endothelial-dependent dilator of pulmonary arteries (PAs). The present study examined the hypothesis that the vasodilator effects of 20-HETE in PAs are due to an elevation of intracellular calcium concentration ([Ca2+]i) and the release of nitric oxide (NO) from bovine PA endothelial cells (BPAECs). BPAECs express cytochrome P-450 4A (CYP4A) protein and produce 20-HETE. 20-HETE dilated PAs preconstricted with U-46619 or norepinephrine and treated with the cytochrome P-450 inhibitor 17-octadecynoic acid and the cyclooxygenase inhibitor indomethacin. The dilator effect of 20-HETE was blocked by the NO synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) or by removal of endothelium. 20-HETE significantly increased [Ca2+]iand NO production in BPAECs. 20-HETE-induced NO release was blunted by removal of extracellular calcium, as well as NO synthase inhibitors (l-NAME). These results suggest that 20-HETE dilates PAs at least in part by increasing [Ca2+]iand NO release in BPAECs.
Nitric oxide synthase inhibition does not alter the reactive hyperemic response in the cutaneous circulation
Authors: Wong Brett J. , Wilkins Brad W. , Holowatz Lacy A. , Minson Christopher T.
Published: March 2015

Reactive hyperemia is the sudden rise in blood flow after release of an arterial occlusion. Currently, the mechanisms mediating this response in the cutaneous circulation are poorly understood. The purpose of this study was to 1) characterize the reactive hyperemic response in the cutaneous circulation and 2) determine the contribution of nitric oxide (NO) to reactive hyperemia. Using laser-Doppler flowmetry, we characterized reactive hyperemia after 3-, 5-, 10-, and 15-min arterial occlusions in 10 subjects. The total hyperemic response was calculated by taking the area under the curve (AUC) of the hyperemic response minus baseline skin blood flow (SkBF) {i.e., total hyperemic response = AUC - [baseline SkBF as %maximal cutaneous vascular conductance (CVCmax) × duration of hyperemic response in s]}. For the characterization protocol, the total hyperemic response significantly increased as the period of ischemia increased from 5 to 15 min ( P < 0.05). However, the 3-min response was not significantly different from the 5-min response. In the NO contribution protocol, two microdialysis fibers were placed in the forearm skin of eight subjects. One site served as a control and was continuously perfused with Ringer solution. The second site was continuously perfused with 10 mM NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NO synthase. CVC was calculated as flux/mean arterial pressure and normalized to maximal blood flow (28 mM sodium nitroprusside). The total hyperemic response in control sites was not significantly different from l-NAME sites after a 5-min occlusion (3,261 ± 890 vs. 2,907 ± 531% CVCmax · s). Similarly, total hyperemic responses in control sites were not different from l-NAME sites (9,155 ± 1,121 vs. 9,126 ± 1,088%CVCmax · s) after a 15-min arterial occlusion. These data suggest that NO does not directly mediate reactive hyperemia and that NO is not produced in response to an increase in shear stress in the cutaneous circulation.
Syncope, cerebral perfusion, and oxygenation
Authors: Van Lieshout Johannes J. , Wieling Wouter , Karemaker John M. , Secher Niels H.
Published: March 2015

During standing, both the position of the cerebral circulation and the reductions in mean arterial pressure (MAP) and cardiac output challenge cerebral autoregulatory (CA) mechanisms. Syncope is most often associated with the upright position and can be provoked by any condition that jeopardizes cerebral blood flow (CBF) and regional cerebral tissue oxygenation (cO2Hb). Reflex (vasovagal) responses, cardiac arrhythmias, and autonomic failure are common causes. An important defense against a critical reduction in the central blood volume is that of muscle activity (“the muscle pump”), and if it is not applied even normal humans faint. Continuous tracking of CBF by transcranial Doppler-determined cerebral blood velocity ( Vmean) and near-infrared spectroscopy-determined cO2Hb contribute to understanding the cerebrovascular adjustments to postural stress; e.g., MAP does not necessarily reflect the cerebrovascular phenomena associated with (pre)syncope. CA may be interpreted as a frequency-dependent phenomenon with attenuated transfer of oscillations in MAP to Vmeanat low frequencies. The clinical implication is that CA does not respond to rapid changes in MAP; e.g., there is a transient fall in Vmeanon standing up and therefore a feeling of lightheadedness that even healthy humans sometimes experience. In subjects with recurrent vasovagal syncope, dynamic CA seems not different from that of healthy controls even during the last minutes before the syncope. Redistribution of cardiac output may affect cerebral perfusion by increased cerebral vascular resistance, supporting the view that cerebral perfusion depends on arterial inflow pressure provided that there is a sufficient cardiac output.
Effect of testosterone on the apneic threshold in women during NREM sleep
Authors: Zhou X. S. , Rowley J. A. , Demirovic F. , Diamond M. P. , Badr M. S.
Published: March 2015

The hypocapnic apneic threshold (AT) is lower in women relative to men. To test the hypothesis that the gender difference in AT was due to testosterone, we determined the AT during non-rapid eye movement sleep in eight healthy, nonsnoring, premenopausal women before and after 10–12 days of transdermal testosterone. Hypocapnia was induced via nasal mechanical ventilation (MV) for 3 min with tidal volumes ranging from 175 to 215% above eupneic tidal volume and respiratory frequency matched to eupneic frequency. Cessation of MV resulted in hypocapnic central apnea or hypopnea depending on the magnitude of hypocapnia. Nadir minute ventilation as a percentage of control (%V˙e) was plotted against the change in end-tidal CO2(Pet CO2 ); %V˙e was given a value of zero during central apnea. The AT was defined as the Pet CO2 at which the apnea closest to the last hypopnea occurred; hypocapnic ventilatory response (HPVR) was defined as the slope of the linear regression V˙e vs. Pet CO2 . Both the AT (39.5 ± 2.9 vs. 42.1 ± 3.0 Torr; P = 0.002) and HPVR (0.20 ± 0.05 vs. 0.33 ± 0.11%V˙e/Torr; P = 0.016) increased with testosterone administration. We conclude that testosterone administration increases AT in premenopausal women, suggesting that the increased breathing instability during sleep in men is related to the presence of testosterone.
Statin therapy restores sympathovagal balance in experimental heart failure
Authors: Pliquett Rainer U. , Cornish Kurtis G. , Zucker Irving H.
Published: March 2015

Inhibitors of hydroxymethylglutaryl-CoA reductase or statins have been shown to alleviate endothelial dysfunction. Their effects on constitutive nitric oxide synthase in the central nervous system may hypothetically affect the autonomic balance in sympathoexcitatory states, such as chronic heart failure (CHF). To address this issue, simvastatin (SIM) (0.3, 1.5, or 3 mg · kg-1 · day-1 po) was given to rabbits with pacing-induced CHF over a 3-wk period. Normal and CHF vehicle-treated rabbits served as controls. Autonomic balance was assessed by measuring heart rate variability, including power spectral analysis (PSA). In addition, changes in resting heart rate were assessed before and after vagal and sympathetic autonomic blockade by atropine and metoprolol, respectively. The SD for all intervals was 8.9 ± 0.7 ms in normal, 4.9 ± 0.6 ms in CHF ( P < 0.01), 3.8 ± 0.6 ms in CHF with 0.3 mg · kg-1 · day-1 SIM ( P < 0.001), 5.7 ± 0.9 in CHF with 1.5 mg · kg-1 · day-1 SIM ( P < 0.05), and 7.2 ± 0.5 in CHF with 3.0 mg · kg-1 · day-1 SIM. Similarly, total power was 40.5 ± 6.3 ms2 in normal, 10.1 ± 3.0 ms2 in CHF ( P < 0.01), 6.0 ± 1.6 ms2 in CHF with 0.3 mg · kg-1 · day-1 SIM ( P < 0.01), 13.2 ± 3.9 ms2 in CHF with 1.5 mg · kg-1 · day-1 SIM ( P < 0.05), and 22.0 ± 3.0 ms2 in CHF with 3.0 mg · kg-1 · day-1 SIM. Both PSA data for low (0.625–0.1875 Hz) and high frequencies (0.1875–0.5625 Hz) showed recovery in CHF animals on medium and high SIM doses without changes in the low-to-high-frequency ratio. SIM beneficially affects autonomic tone in CHF as seen by the reversal of depressed HRV and total power of PSA. These data have important implications for the treatment of patients with autonomic imbalance.
Transient induction of cyclin A in loaded chicken skeletal muscle
Authors: Flück Martin , Kitzmann Magali , Däpp Christoph , Chiquet Matthias , Booth Frank W. , Fernandez Anne
Published: March 2015

Cell proliferation is believed to contribute to the increased synthesis rate during load-induced growth of avian anterior latissimus dorsi (ALD) skeletal muscle, but the relative contribution of different cell types to this proliferative response and the time course of cell activation are not well documented. The present investigation measured the abundance and localization of cyclin A protein, which is uniquely present in proliferating cells and required for the entry of vertebrate cells into the DNA synthesis phase during the time course of chicken ALD loading. Total protein content in 1.5-, 7-, and 13-day loaded ALD increased by 60, 191, and 294%, respectively. Immunoblotting analysis identified that cyclin A protein per total protein was dramatically increased in ALD muscle after 1.5 days of loading but returned to control level at 7 days. In vitro kinase assays demonstrated a corresponding massive activation of the cyclin A-regulated, cyclin-dependent kinase 2 but not of cyclin-dependent kinase 2 protein level in muscle homogenates after 1.5 days of muscle loading. Immunofluorescence experiments demonstrated that the increase of cyclin A in 1.5 days of loaded ALD was primarily confined to nuclei of interstitial cells (92%) but was also found in fiber-associated cells (8%). In situ hybridization demonstrated an increased number of nuclei of interstitial cells expressing collagen I transcripts after 1.5 days of loading. These data show that the cell cycle protein cyclin A is induced in fiber-associated cells during the early growth response in loaded ALD but also implicate an activation of interstitial cells as playing an early role in this model for muscle growth.
Serum leptin responses after acute resistance exercise protocols
Authors: Zafeiridis A. , Smilios I. , Considine R. V. , Tokmakidis S. P.
Published: March 2015

This study examined the acute effects of maximum strength (MS), muscular hypertrophy (MH), and strength endurance (SE) resistance exercise protocols on serum leptin. Ten young lean men (age = 23 ± 4 yr; body weight = 79.6 ± 5.2 kg; body fat = 10.2 ± 3.9%) participated in MS [4 sets × 5 repetitions (reps) at 88% of 1 repetition maximum (1 RM) with 3 min of rest between sets], MH (4 sets × 10 reps at 75% of 1 RM with 2 min of rest between sets), SE (4 sets × 15 reps at 60% of 1 RM with 1 min of rest between sets), and control (C) sessions. Blood samples were collected before and immediately after exercise and after 30 min of recovery. Serum leptin at 30 min of recovery exhibited similar reductions from baseline after the MS (−20 ± 5%), MH (−20 ± 4%), and SE (−15 ± 6%) protocols that were comparable to fasting-induced reduction in the C session (−12 ± 3%) ( P < 0.05). Furthermore, no differences were found in serum leptin among the MS, MH, SE, and C sessions immediately after exercise and at 30 min of recovery ( P > 0.05). Cortisol was higher ( P < 0.05) after the MH and SE protocols than after the MS and C sessions. Glucose and growth hormone were higher ( P < 0.05) after exercise in the MS, MH, and SE protocols than after the C session. In conclusion, typical resistance exercise protocols designed for development of MS, MH, and SE did not result in serum leptin changes when sampled immediately or 30 min postexercise.
Medullary raphe neuron activity is altered during fictive cough in the decerebrate cat
Authors: Baekey David M. , Morris Kendall F. , Nuding Sarah C. , Segers Lauren S. , Lindsey Bruce G. , Shannon Roger
Published: March 2015

Chemical lesions in the medullary raphe nuclei region influence cough. This study examined whether firing patterns of caudal medullary midline neurons were altered during cough. Extracellular neuron activity was recorded with microelectrode arrays in decerebrated, neuromuscular-blocked, ventilated cats. Cough-like motor patterns (fictive cough) in phrenic and lumbar nerves were elicited by mechanical stimulation of the intrathoracic trachea. Discharge patterns of respiratory and nonrespiratory-modulated neurons were altered during cough cycles (58/133); 45 increased and 13 decreased activity. Fourteen cells changed firing rate during the inspiratory and/or expiratory phases of cough. Altered patterns in 43 cells were associated with the duration of, or extended beyond, the cough episodes. The different response categories suggest that multiple factors influence the discharge patterns during coughing: e.g., respiratory-modulated and tonic inputs and intrinsic connections. These results suggest involvement of midline neurons (i.e., raphe nuclei) in the cough reflex.
Autonomic and vascular responses to reduced limb perfusion
Authors: Daley Joseph C. , Khan Mazhar H. , Hogeman Cynthia S. , Sinoway Lawrence I.
Published: March 2015

The purpose of this study was to examine hemodynamic responses to graded muscle reflex engagement in human subjects. We studied seven healthy human volunteers [24 ± 2 (SE) yr old; 4 men, 3 women] performing rhythmic handgrip exercise [40% maximal voluntary contraction (MVC)] during ambient and positive pressure exercise (+10 to +50 mmHg in 10-mmHg increments every minute). Muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and mean blood velocity were recorded. Plasma lactate, hydrogen ion concentration, and oxyhemoglobin saturation were measured from venous blood. Ischemic exercise resulted in a greater rise in both MSNA and MAP vs. nonischemic exercise. These heightened autonomic responses were noted at +40 and +50 mmHg. Each level of positive pressure was associated with an immediate fall in flow velocity and forearm perfusion pressure. However, during each minute, perfusion pressure increased progressively. For positive pressure of +10 to +40 mmHg, this was associated with restoration of flow velocity. However, at +50 mmHg, flow was not restored. This inability to restore flow was seen at a time when the muscle reflex was clearly engaged (increased MSNA). We believe that these findings are consistent with the hypothesis that before the muscle reflex is clearly engaged, flow to muscle is enhanced by a process that raises perfusion pressure. Once the muscle reflex is clearly engaged and MSNA is augmented, flow to muscle is no longer restored by a similar rise in perfusion pressure, suggesting that active vasoconstriction within muscle is occurring at +50 mmHg.
The off rate of Ca2+from troponin C is regulated by force-generating cross bridges in skeletal muscle
Authors: Wang Ying , Kerrick W. Glenn L.
Published: March 2015

The effects of dissociation of force-generating cross bridges on intracellular Ca2+, pCa-force, and pCa-ATPase relationships were investigated in mouse skeletal muscle. Mechanical length perturbations were used to dissociate force-generating cross bridges in either intact or skinned fibers. In intact muscle, an impulse stretch or release, a continuous length vibration, a nonoverlap stretch, or an unloaded shortening during a twitch caused a transient increase in intracellular Ca2+compared with that in isometric controls and resulted in deactivation of the muscle. In skinned fibers, sinusoidal length vibrations shifted pCa-force and pCa-actomyosin ATPase rate relationships to higher Ca2+concentrations and caused actomyosin ATPase rate to decrease at submaximal Ca2+and increase at maximal Ca2+activation. These results suggest that dissociation of force-generating cross bridges during a twitch causes the off rate of Ca2+from troponin C to increase (a decrease in the Ca2+affinity of troponin C), thus decreasing the Ca2+sensitivity and resulting in the deactivation of the muscle. The results also suggest that the Fenn effect only exists at maximal but not submaximal force-activating Ca2+concentrations.
PGE2 sensitizes cultured pulmonary vagal sensory neurons to chemical and electrical stimuli
Authors: Kwong Kevin , Lee Lu-Yuan
Published: March 2015

Mediators of inflammation, such as PGE2, are known to sensitize the airways to inhaled irritants and circulating autacoids. Evidence from in vivo studies has shown the involvement of vagal pulmonary C-fiber afferents in the PGE2-elicited airway hypersensitivity. However, whether PGE2 acts directly on these sensory nerves is unclear. The present study aimed to investigate whether PGE2 has direct potentiating effects on nodose and jugular pulmonary C neurons cultured from adult Sprague-Dawley rats and, if so, determine whether the EP2 prostanoid receptor is involved. Pulmonary neurons were identified by retrograde labeling with a fluorescent tracer 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate. Using perforated patch-clamp technique, our results showed that 1) PGE2 pretreatment (1 μM) increased the whole cell current density elicited by capsaicin and phenylbiguanide, chemical agents known to stimulate pulmonary C fibers; 2) selective activation of the EP2 prostanoid receptor by butaprost (3–10 μM) increased the whole cell current density elicited by capsaicin; and 3) PGE2, as well as butaprost, increased the number of action potentials evoked by current injection. Therefore, we conclude that PGE2 directly sensitizes vagal pulmonary C neurons to chemical and electrical stimulation. Furthermore, butaprost modulates the neurons in a manner similar to that of PGE2, suggesting that the effects of PGE2 are mediated, at least in part, through the EP2 prostanoid receptor.
Preventing annoyance from odors in spaceflight: a method for evaluating the sensory impact of rodent housing
Authors: Dalton P. , Gould M. , Girten B. , Stodieck L. S. , Bateman T. A.
Published: March 2015

For the scientific community, the ability to fly mice under weightless conditions in space offers several advantages over the use of rats. These advantages include the option of testing a range of transgenic animals, the ability to increase the number of animals that can be flown, and reduced demands on shuttle resources (food, water, animal mass) and crew time (for water refill). Mice have been flown in animal enclosure module (AEM) hardware only once [Space Shuttle Transport System (STS)-90] and were dissected early in the mission, whereas rats have been flown in the AEM on >20 missions. This has been due, in part, to concerns that strong and annoying odors from mouse urine (vs. rat urine) will interfere with crew performance in the shuttle middeck. To screen and approve mice for flight, a method was developed to evaluate the odor containment performance of AEMs housing female C57BL/6J mice compared with AEMs housing Sprague-Dawley rats across a 21-day test period. Based on the results of this test, consensus was reached that mice could fly in the AEM hardware for up to 17 days (including prelaunch and contingency) and that the AEM hardware would likely contain odors beyond this duration. Human sensory and electronic nose analysis of the AEMs postflight demonstrated their success in containing odors from mice for the mission duration of STS-108 (13 days). Although this paper focuses specifically on odor evaluations for the space shuttle, the concern is applicable to any confined, closed-system environment for human habitation.
Cycling as a novel approach to resistance training increases muscle strength, power, and selected functional abilities in healthy older women
Authors: Macaluso Andrea , Young Archie , Gibb Katie S. , Rowe David A. , De Vito Giuseppe
Published: March 2015

Cycling on a mechanically braked cycle ergometer was used as a novel approach to compare the effects of three different 16-wk resistance-training programs on isometric force, power output, and selected functional abilities in 31 healthy 65- to 74-yr-old women. Training was conducted three times per week. During each session, individuals of the speed group performed 8 sets of 16 pedal revolutions at 40% of the maximal resistance to complete two revolutions (2 RM); strength group performed 8 sets of 8 revolutions at 80% of 2 RM; and combination group performed 4 sets of 16 revolutions at 40% and 4 sets of 8 revolutions at 80% of 2 RM. During each set, all participants were required to pedal as fast as possible with a 2-min interval between sets. All training groups significantly increased force, power, and functional abilities (maximal treadmill walking speed, vertical jumping, and box stepping) at week 8 (in the range from 6.5 to 20.8%) with no further improvement at week 16 (except maximal treadmill walking speed), but no significant differences were observed between the three groups. The novel approach to performing both low- and high-resistance training, based on the use of a cycle ergometer, has been shown to be effective in improving strength, power, and functional abilities in a group of healthy women. Even fit older women can still improve in functional abilities. Interestingly, the “high-speed” and “low-speed” programs induced an increase in both power and strength of similar magnitude.