The long-term objectives of the Principal Investigator are to evaluate reflex mechanisms that regulate the cardiovascular system in humans. The investigator has recently demonstrated that head-down neck flexion (HDNF) increases muscle sympathetic nerve activity (MSNA). This finding suggested a role of the vestibular system in regulating MSNA. The overall hypothesis to be evaluated in this project is that the vestibular system plays an important role in the regulation of the sympathetic nervous system in humans. This hypothesis will be evaluated by recording MSNA in humans during activation of the vestibular system by different head movements. In this proposal the following hypotheses will be tested: 1. Increases in MSNA during HDNF are due to vestibular activation. 2. Otolith organs but not semicircular canals elicit increases in MSNA. 3. Activation of the vestibulosympathetic reflex modulates MSNA elicited by other cardiovascular reflexes. To test these hypotheses, studies with the following specific aims are proposed: 1. To determine MSNA responses to HDNF during different levels and durations of neck flexion, and performed in different body positions. 2. To determine MSNA responses during dynamic head movements which activate both the otolith organs and semicircular canals. 3. To determine the interaction of HDNF (vestibulosympathetic reflex) with other cardiovascular reflexes (e.g., arterial baroreflex) on MSNA in humans. The design of these studies will provide new knowledge regarding vestibular regulation of sympathetic activity in humans. These findings may have important implications in understanding the cause of orthostatic intolerance in otherwise healthy subjects and why orthostatic intolerance is more prevalent in the elderly and in individuals following prolonged exposure to microgravity.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Respiratory and Applied Physiology Study Section (RAP)
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Pennsylvania State University
Internal Medicine/Medicine
Schools of Medicine
United States
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Cook, Jonathan S; Ray, Chester A (2009) Modulation of muscle sympathetic nerve activity to muscle heating during dynamic exercise. Am J Physiol Regul Integr Comp Physiol 296:R1439-44
Momen, Afsana; Leuenberger, Urs A; Ray, Chester A et al. (2003) Renal vascular responses to static handgrip: role of muscle mechanoreflex. Am J Physiol Heart Circ Physiol 285:H1247-53
Khan, Mazhar H; Kunselman, Allen R; Leuenberger, Urs A et al. (2002) Attenuated sympathetic nerve responses after 24 hours of bed rest. Am J Physiol Heart Circ Physiol 282:H2210-5
Imadojemu, V A; Lott, M E; Gleeson, K et al. (2001) Contribution of perfusion pressure to vascular resistance response during head-up tilt. Am J Physiol Heart Circ Physiol 281:H371-5
Doerzbacher, K J; Ray, C A (2001) Muscle sympathetic nerve responses to physiological changes in prostaglandin production in humans. J Appl Physiol 90:624-9