Determinants of skin sympathetic nerve responses to isometric exercise. J Appl Physiol 100: 1043-1048, 2006. First published November 10, 2005 doi:10.1152/japplphysiol.00579.2005.-Exercise-induced increases in skin sympathetic nerve activity (SSNA) are similar between isometric handgrip (IHG) and leg extension (IKE) performed at 30% of maximal voluntary contraction (MVC). However, the precise effect of exercise intensity and level of fatigue on this relationship is unclear. This study tested the following hypotheses: 1) exercise intensity and fatigue level would not affect the magnitude of exercise-induced increase in SSNA between IHG and IKE, and 2) altering IHG muscle mass would also not affect the magnitude of exercise-induced increase in SSNA. In protocol 1, SSNA (peroneal microneurography) was measured during baseline and during the initial and last 30 s of isometric exercise to volitional fatigue in 12 subjects who randomly performed IHG and IKE bouts at 15, 30, and 45% MVC. In protocol 2, SSNA was measured in eight subjects who performed one-arm IHG at 30% MVC with the addition of IHG of the contralateral arm in 10-s intervals for 1 min. Exercise intensity significantly increased SSNA responses during the first 30 s of IHG (34 Ϯ 13, 70 Ϯ 11, and 92 Ϯ 13% change from baseline) and IKE (30 Ϯ 17, 69 Ϯ 12, and 76 Ϯ 13% change from baseline) for 15, 30, and 45% MVC. During the last 30 s of exercise to volitional fatigue, there were no significant differences in SSNA between exercise intensities or limb. SSNA did not significantly change between onearm and two-arm IHG. Combined, these data indicate that exerciseinduced increases in SSNA are intensity dependent in the initial portion of isometric exercise, but these differences are eliminated with the development of fatigue. Moreover, the magnitude of exerciseinduced increase in SSNA responses is not dependent on either muscle mass involved or exercising limb. skin blood flow; sweat rate; and microneurography SYMPATHETIC OUTFLOW TO THE skin is increased during isometric and rhythmic exercise (7,12,26). This exercise-induced increase in skin sympathetic nerve activity (SSNA) is controlled by the engagement of central command and activation of muscle mechanoreceptors, and it may be controlled, under very specific conditions, by activation of muscle metaboreceptors (11). Unlike muscle sympathetic nerve activity, the precise determinants of exercise-induced increases in SSNA are equivocal.Previous studies indicate that the exercise-induced increases in SSNA are intensity dependent to ϳ45% of maximal voluntary contraction (MVC) and that level of effort modulates SSNA responses to isometric exercise (27,28). Seals (20) observed another determinant to exercise-induced increases in SSNA by demonstrating that the level of fatigue may be a prime factor regardless of exercise intensity. In these experiments, he observed no difference in SSNA responses between higher exercise intensities (i.e., 45 and 60% MVC) during isometric handgrip (IHG) at and near volitional fatigu...

Activation of the vestibular otolith organs with head-down rotation (HDR) increases muscle sympathetic nerve activity (MSNA) in humans. Previously, we demonstrated this vestibulosympathetic reflex (VSR) elicits increases in MSNA during baroreflex unloading (i.e., lower body negative pressure) in humans. Whether such an effect persists during baroreflex loading is unknown. We tested the hypothesis that the ability of the VSR to increase MSNA is preserved during baroreflex unloading and inhibited during baroreflex loading. Ten subjects (26 +/- 1 yr) performed three trials of HDR to activate the VSR. These trials were performed after a period of sustained saline (control), nitroprusside (baroreflex unloading: 0.8-1.0 microg.kg(-1).min(-1)), and phenylephrine (baroreflex loading: 0.6-0.8 microg.kg(-1).min(-1)) infusion. Nitroprusside infusion decreased (Delta7 +/- 1 mmHg, where Delta is change; P < 0.001) and phenylephrine infusion increased mean arterial pressure (Delta8 +/- 1 mmHg; P < 0.001) at rest. HDR performed during the control [Delta3 +/- 2 bursts/min, Delta314 +/- 154 arbitrary units (au) total activity, Delta41 +/- 18% total activity; P < 0.05] and nitroprusside trials [Delta5 +/- 2 bursts/min, Delta713 +/- 241 au total activity, Delta49 +/- 20% total activity; P < 0.05] increased MSNA similarly despite significantly elevated levels at rest (13 +/- 2 to 26 +/- 3 bursts/min) in the latter. In contrast, HDR performed during the phenylephrine trial failed to increase MSNA (Delta0 +/- 1 bursts/min, Delta-15 +/- 33 au total activity, Delta-8 +/- 21% total activity). These results confirm previous findings that the ability of the VSR to increase MSNA is preserved during baroreflex unloading. In contrast, the ability of the VSR to increase MSNA is abolished during baroreflex loading. These results provide further support for the concept that the VSR may act primarily to defend against hypotension in humans.

Blood lipids may detrimentally affect autonomic and circulatory control. We tested the hypotheses that acute elevations in free fatty acids and triglycerides (acute hyperlipidemia) impair baroreflex control of cardiac period [cardiovagal baroreflex sensitivity (BRS)] and muscle sympathetic nerve activity (MSNA: sympathetic BRS), increase MSNA at rest, and augment physiological responses to exercise. Eighteen young adults were examined in this randomized, double-blinded, and placebo-controlled study. BRS was determined using the modified Oxford technique before (pre) and 60 min (post) after initiating infusion of Intralipid (0.8 ml x m(-2) x min(-1)) and heparin (1,000 U/h) (experimental; n = 12) to induce acute hyperlipidemia, or saline (0.8 ml x m(-2) x min(-1)) and heparin (1,000 U/h) (control; n = 6). Responses to isometric handgrip to fatigue (IHG) were also determined. Blood pressure increased more (P < 0.05) in experimental than control subjects during the infusion. MSNA at rest (14 +/- 2 vs. 11 +/- 1 bursts/min), cardiovagal (19.8 +/- 1.8 vs. 19.1 +/- 2.4 ms/mmHg pre and post, respectively) and sympathetic BRS (-5.5 +/- 0.6 vs. -5.2 +/- 0.4 au x beat(-1) x mmHg(-1)), and the neural and cardiovascular responses to IHG were unchanged by acute hyperlipidemia (pre vs. post) in experimental subjects. Similarly, MSNA at rest (10 +/- 2 vs. 12 +/- 2 bursts/min), cardiovagal (22.1 +/- 4.0 vs. 21.0 +/- 4.6 ms/mmHg) and sympathetic BRS (-5.8 +/- 0.5 vs. -5.5 +/- 0.5 au x beat(-1) x mmHg(-1)), and the neural and cardiovascular responses to IHG were unchanged by the infusion in control subjects. These data do not provide experimental support for the concept that acute hyperlipidemia impairs reflex cardiovagal or sympathetic regulation in humans.

Dyckman DJ, Sauder CL, Ray CA. Effects of short-term and prolonged bed rest on the vestibulosympathetic reflex. Am J Physiol Heart Circ Physiol 302: H368 -H374, 2012. First published October 21, 2011 doi:10.1152/ajpheart.00193.2011.-The mechanism(s) for post-bed rest (BR) orthostatic intolerance is equivocal. The vestibulosympathetic reflex contributes to postural blood pressure regulation. It was hypothesized that muscle sympathetic nerve responses to otolith stimulation would be attenuated by prolonged head-down BR. Arterial blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), and peripheral vascular conductance were measured during head-down rotation (HDR; otolith organ stimulation) in the prone posture before and after short-duration (24 h; n ϭ 22) and prolonged (36 Ϯ 1 day; n ϭ 8) BR. Head-up tilt at 80°was performed to assess orthostatic tolerance. After short-duration BR, MSNA responses to HDR were preserved (⌬5 Ϯ 1 bursts/min, ⌬53 Ϯ 13% burst frequency, ⌬65 Ϯ 13% total activity; P Ͻ 0.001). After prolonged BR, MSNA responses to HDR were attenuated ϳ50%. MSNA increased by ⌬8 Ϯ 2 vs. ⌬3 Ϯ 2 bursts/min and ⌬83 Ϯ 12 vs. ⌬34 Ϯ 22% total activity during HDR before and after prolonged BR, respectively. Moreover, these results were observed in three subjects tested again after 75 Ϯ 1 days of BR. This reduction in MSNA responses to otolith organ stimulation at 5 wk occurred with reductions in head-up tilt duration. These results indicate that prolonged BR (ϳ5 wk) unlike short-term BR (24 h) attenuates the vestibulosympathetic reflex and possibly contributes to orthostatic intolerance following BR in humans. These results suggest a novel mechanism in the development of orthostatic intolerance in humans. blood pressure; autonomic nervous system; muscle sympathetic nerve activity; hypotension ORTHOSTATIC INTOLERANCE (OI) is the inability to maintain blood pressure and cerebral perfusion while in the upright position. Moreover, the failure to maintain blood pressure in the upright posture is associated with increased mortality (26). Head-down bed rest (BR) is used to simulate microgravity and physical deconditioning and to elicit OI (13). Mechanisms believed to contribute to the development of OI with BR include: impaired vagal baroreflex responses (5), an inadequate increase in sympathetic discharge (18, 42), cardiac atrophy (24), an inability to increase peripheral vascular resistance (3, 25), and hypovolemia (29). Studies indicate that alterations in sympathetic nerve activity contribute to the development of OI (13,18,25,42). Hypotensive episodes during head-up tilt appear to be closely related to lack of increased muscle sympathetic nerve activity (MSNA) (25). MSNA is attenuated during tilt following 14 days of BR in subjects that experienced OI (42). Despite considerable research on this topic, the mechanisms for OI have been an enigma. One possible mechanism for the development of OI after BR that has not been examined is an alteration of the vestibulosympathetic reflex (VSR).Data exist demon...

Sedimentation equilibrium studies show that the Escherichia coli cyclic AMP receptor protein (CAP) and RNA polymerase holoenzyme associate to form a 2:2 complex in vitro. No complexes of lower stoichiometry (1:1, 2:1, 1:2) were detected over a wide range of CAP and RNA polymerase concentrations, suggesting that the interaction is highly cooperative. The absence of higher stoichiometry complexes, even in the limit of high [protein], suggests that the 2:2 species represents binding saturation for this system. The 2:2 pattern of complex formation is robust. A lower-limit estimate of the formation constant in our standard buffer (40 mM Tris (pH 7.9), 10 mM MgCl 2 , 0.1 mM dithiothreitol, 5% glycerol, 100 mM KCl) is 2 ؋ 10 20 M ؊3 . The qualitative pattern of association is unchanged over the temperature range 4°C < T < 20°C, by substitution of glutamate for chloride as the dominant anion, or on addition of 20 M cAMP to the reaction mix. These results limit the possible mechanisms of CAP-polymerase association. In addition, they support the idea that CAP binding may influence the availability of the monomeric form of RNA polymerase that mediates transcription at many promoters.