The overall objective of Project 4 of this Program Project Grant is to further our understanding of how activation of the vestibular system contributes to sympathetic and cardiopulmonary regulation during orthostatic stress in humans. We hypothesize that the vestibular reflex activation of sympathetic nerve activity, and subsequent peripheral and visceral vascular responses, and respiratory responses are attenuated in humans with a predisposition to orthostatic intolerance (i.e., idiopathic orthostatic hypotension, vestibular deficient subjects, aged, and highly trained endurance athletes). During the past five years, we have gained new insights regarding vestibular regulation of sympathetic nerve activity and respiration in humans. These studies have demonstrated that engagement of the otolith organs increases muscle sympathetic nerve activity while engagement of the semicircular canals increases respiration. Furthermore, studies in older subjects demonstrate an attenuation of both the vestibulosympathetic and vestibulorespiratory reflexes. Because aging is associated with increased orthostatic intolerance, these findings suggest that these vestibular reflexes may play an important role in orthostatic intolerance. We will test the following specific aims in healthy sedentary controls and subjects with a predisposition to orthostatic intolerance: To examine sympathetic and hemodynamic responses to otolith organ stimulation. To examine peripheral (skeletal muscle) and visceral (renal and mesenteric) vascular responses to vestibular stimulation. To examine respiratory responses to vestibular stimulation. The design of these studies will provide new knowledge regarding vestibular regulation of the sympathetic nervous system and respiration in humans. Additionally, these studies will address the hypotheses that the vestibular system contributes to blood pressure regulation during orthostatic stress and that attenuation of these reflexes contributes to impaired postural blood pressure regulation. Results from these studies will provide a better understanding of a heretofore overlooked but important afferent input to efferent regulation of sympathetic nerve activity and respiration during postural stress.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL077670-05
Application #
7643257
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
5
Fiscal Year
2008
Total Cost
$441,430
Indirect Cost
Name
Pennsylvania State University
Department
Type
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Cui, Jian; Sinoway, Lawrence I (2014) Cardiovascular responses to heat stress in chronic heart failure. Curr Heart Fail Rep 11:139-45
Ray, Chester A; Sauder, Charity L; Chin-Sang, Stephanie A et al. (2013) Is there diurnal variation of the vestibulosympathetic reflex: implications for orthostatic hypotension. Am J Physiol Heart Circ Physiol 305:H1555-9
Dyckman, Damian J; Sauder, Charity L; Ray, Chester A (2012) Effects of short-term and prolonged bed rest on the vestibulosympathetic reflex. Am J Physiol Heart Circ Physiol 302:H368-74
Dyckman, Damian J; Sauder, Charity L; Ray, Chester A (2011) Glycerol-induced fluid shifts attenuate the vestibulosympathetic reflex in humans. Am J Physiol Regul Integr Comp Physiol 300:R630-4
Cui, Jian; Leuenberger, Urs A; Blaha, Cheryl et al. (2011) Effect of P2 receptor blockade with pyridoxine on sympathetic response to exercise pressor reflex in humans. J Physiol 589:685-95
Krishnan, Anandi; Lucassen, Elisabeth B; Hogeman, Cindy et al. (2011) Effects of limb posture on reactive hyperemia. Eur J Appl Physiol 111:1415-20
Cook, Jonathan S; Sauder, Charity L; Ray, Chester A (2011) Melatonin differentially affects vascular blood flow in humans. Am J Physiol Heart Circ Physiol 300:H670-4
Greaney, Jody L; Ray, Chester A; Prettyman, Allen V et al. (2010) Influence of increased plasma osmolality on sympathetic outflow during apnea. Am J Physiol Regul Integr Comp Physiol 299:R1091-6
Moradkhan, Raman; Sinoway, Lawrence I (2010) Revisiting the role of oxygen therapy in cardiac patients. J Am Coll Cardiol 56:1013-6
Wilson, Thad E; Monahan, Kevin D; Fogelman, Amy et al. (2010) Aerobic training improves in vivo cholinergic responsiveness but not sensitivity of eccrine sweat glands. J Invest Dermatol 130:2328-30

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