The long-term objective of the Principal Investigator is to evaluate vestibular reflex mechanisms that regulate the cardiovascular system in humans. During the past funding period, we demonstrated that activation of the otolith organs mediated prompt and marked increases in sympathetic nerve activity and limb vascular resistance. The main hypothesis for this project is that the vestibulosympathetic reflex participates importantly in orthostasis by activating the sympathetic nervous system in humans. It is hypothesized that attenuations in the vestibulosympathetic reflex contributes to orthostatic intolerance in humans. To test these hypotheses, we propose studies with the following specific aims: 1. To determine muscle sympathetic nerve activity (MSNA) responses during dynamic pitch rotation. Transition from the supine to upright posture and ambulation dynamically stimulate the otolith organs Therefore, it is important to determine whether dynamic activation of the otolith organs elicits increases in sympathetic vasoconstrictor outflow. We hypothesize greater increases in MSNA will be elicited by dynamic rather than static engagement of the otolith organs. 2. To determine MSNA responses to otolith organ stimulation in the prone, sitting, and upright positions. Because postural blood pressure control is most important in the upright posture, we will test the vestibulosympathetic reflex during head rotations in the sitting and standing positions. We hypothesize that increases in MSNA by the vestibulosympathetic reflex via head-down rotation is independent of body posture. 3. To determine visceral vascular responses to static head-down rotation. Because visceral vascular vasoconstriction contributes importantly to postural blood pressure regulation, we hypothesize that vestibular activation will mediate increases in visceral vascular resistance. 4. To examine sympathetic and hemodynamic responses to otolith organ stimulation in subjects with a predisposition to orthostatic intolerance. We hypothesize that MSNA responses will be attenuated and blood pressure reduced during activation of the vestibulosympathetic in subjects with orthostatic intolerance (i.e., vestibular deficient and idiopathic orthostatic hypotension subjects, and endurance trained athletes). The design of these studies will increase our understanding of how the vestibular system contributes to orthostatic blood pressure regulation in humans. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC006459-08
Application #
6870181
Study Section
Respiratory Physiology Study Section (RESP)
Program Officer
Platt, Christopher
Project Start
1998-04-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2007-03-31
Support Year
8
Fiscal Year
2005
Total Cost
$272,454
Indirect Cost
Name
Pennsylvania State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
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
Kuipers, Nathan T; Sauder, Charity L; Kearney, Matthew L et al. (2009) Interactive effect of aging and local muscle heating on renal vasoconstriction during isometric handgrip. Am J Physiol Renal Physiol 297:F327-32
Carter, Jason R; Ray, Chester A (2009) Sympathetic neural responses to mental stress: responders, nonresponders and sex differences. Am J Physiol Heart Circ Physiol 296:H847-53
Behnke, Bradley J; Zawieja, David C; Gashev, Anatoliy A et al. (2008) Diminished mesenteric vaso- and venoconstriction and elevated plasma ANP and BNP with simulated microgravity. J Appl Physiol 104:1273-80
Lesniewski, Lisa A; Donato, Anthony J; Behnke, Bradley J et al. (2008) Decreased NO signaling leads to enhanced vasoconstrictor responsiveness in skeletal muscle arterioles of the ZDF rat prior to overt diabetes and hypertension. Am J Physiol Heart Circ Physiol 294:H1840-50
Lawrence, Johnathan E; Ray, Chester A; Carter, Jason R (2008) Vestibulosympathetic reflex during the early follicular and midluteal phases of the menstrual cycle. Am J Physiol Endocrinol Metab 294:E1046-50
Carter, Jason R; Ray, Chester A (2008) Sympathetic responses to vestibular activation in humans. Am J Physiol Regul Integr Comp Physiol 294:R681-8
Kuipers, Nathan T; Sauder, Charity L; Carter, Jason R et al. (2008) Neurovascular responses to mental stress in the supine and upright postures. J Appl Physiol 104:1129-36
Newcomer, S C; Sauder, C L; Kuipers, N T et al. (2008) Effects of posture on shear rates in human brachial and superficial femoral arteries. Am J Physiol Heart Circ Physiol 294:H1833-9

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