Project 1: Autonomic Determinants of Ortliostatic Tolerance David Robertson, IVI.D., Project Leader Maintenance of upright posture is a challenge for the autonomic nervous system. Even mild perturbation of autonomic control mechanisms can alter orthostatic tolerance. When one or more determinants of orthostatic intolerance is impaired, orthostatic intolerance or syncope can supervene. Project 1 focuses on one such determinant which escaped detection until it was discovered during studies earlier in this PPG project. The effect was a surprisingly large pressor response elicited by oral ingestion of 16 oz of water. The systolic pressor effect averaged ~40 mm Hg in patients with baroreflex impairment but some had smaller responses and a few had increases greater than 100 mm Hg. These remarkable pressor effects were not predicted by classical physiology, but have been subsequently replicated and their magnitude confirmed by multiple investigators. We have termed this the "osmopressor response (OPR)". it seems to signal an important but heretofore unrecognized mechanism at work in human cardiovascular regulation. We have made progress in understanding the physiological basis of water's pressor effect, and hypothesize that the osmopressor response (OPR) is an important autonomic determinant of orthostatic tolerance in human subjects. The goal of Project 1 is to elucidate mechanisms underlying OPR function, to identify OPR's potential role in normal and pathological conditions, and to find ways to harness it to benefit human health. Project Specific Aims are: (1-2) To elucidate the structure and function of the osmopressor response (OPR) (3) To identify the role of the OPR in health and disease (4) To harness the OPR mechanism to benefit health

Public Health Relevance

Control of blood pressure is important for health. We recently discovered an unexpected way that the body uses water drinking to control blood pressure. It is a powerful effect in some but not all people. If we can understand how this works and find new drugs that can affect it, we might be able through simple and inexpensive measures to prevent high and low blood pressure, and help prevent people from passing out.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL056693-17
Application #
8458074
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
17
Fiscal Year
2013
Total Cost
$288,198
Indirect Cost
$74,692
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Biaggioni, Italo; Calhoun, David A (2016) Sympathetic Activity, Hypertension, and The Importance of a Good Night's Sleep. Hypertension 68:1338-1339
Harder, René; Malow, Beth A; Goodpaster, R Lucas et al. (2016) Heart rate variability during sleep in children with autism spectrum disorder. Clin Auton Res 26:423-432
Mar, Philip L; Nwazue, Victor; Black, Bonnie K et al. (2016) Valsalva Maneuver in Pulmonary Arterial Hypertension: Susceptibility to Syncope and Autonomic Dysfunction. Chest 149:1252-60
Shibao, Cyndya A; Celedonio, Jorge E; Ramirez, Claudia E et al. (2016) A Common CD36 Variant Influences Endothelial Function and Response to Treatment with Phosphodiesterase 5 Inhibition. J Clin Endocrinol Metab 101:2751-8
Adefurin, Abiodun; Darghosian, Leon; Okafor, Chimalum et al. (2016) Alpha2A adrenergic receptor genetic variation contributes to hyperglycemia after myocardial infarction. Int J Cardiol 215:482-6
Raj, Satish R (2016) Row, row, row your way to treating postural tachycardia syndrome. Heart Rhythm 13:951-2
Joy, Nino G; Perkins, Jennifer M; Mikeladze, Maia et al. (2016) Comparative effects of acute hypoglycemia and hyperglycemia on pro-atherothrombotic biomarkers and endothelial function in non-diabetic humans. J Diabetes Complications 30:1275-81
Lateef, Dalya M; Xiao, Cuiying; Brychta, Robert J et al. (2016) Bombesin-like receptor 3 regulates blood pressure and heart rate via a central sympathetic mechanism. Am J Physiol Heart Circ Physiol 310:H891-8
Harder, Rene; Diedrich, Andre; Whitfield, Jonathan S et al. (2016) Smart Multi-Frequency Bioelectrical Impedance Spectrometer for BIA and BIVA Applications. IEEE Trans Biomed Circuits Syst 10:912-9
Iwuchukwu, Otito F; Ramirez, Andrea H; Shi, Yaping et al. (2016) Genetic determinants of variability in warfarin response after the dose-titration phase. Pharmacogenet Genomics 26:510-516

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