The overall long-term goal of this project remains to study interactions behween autonomic and metabolic mechanisms involved in cardiovascular regulation. In this funding period the focus of this application is to test the hypothesis that sympathetic activation contributes to impaired nitric oxide (NO) function in obesity hypertension. Impaired NO function is present in obesity and is proposed as a primary mechanism contributing to the high prevalence of hypertension in this condition. We have also documented impaired NO-mediated vasodilation in """"""""intact"""""""" obese hypertensives, but NO impairment is no longer evident if autonomic influences are removed with ganglionic blockade. We propose, therefore, that sympathetic activation is the primary event in obesity hypertension, leading to secondary impairment of NO function. If our hypothesis is true, then the impaired NO function present in obesity can be restored with acute autonomic withdrawal (Specific Aim 1);conversely, impaired NO function can me mimicked in lean controls by adrenergic stimulation (Specific Aim 2), and;targeting sympathetic activation in the treatment of obesity hypertension will improve NO function and related derangements (Specific Aim 3). Our goal is to improve our understanding of the pathophysiological interaction between nitric oxide and the autonomic nervous system, and to provide the knowledge base that will ultimately impact the treatment of obesity hypertension.

Public Health Relevance

Obesity-associated hypertension is a growing medical problem contributing to greater health care costs. Our proposal will investigate how two important systems involved in blood pressure regulation, the autonomic nervous system and nitric oxide, contribute to obesity hypertension. Our ultimate goal is to apply this knowledge to improve the treatment of obesity hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL056693-16
Application #
8293467
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
16
Fiscal Year
2012
Total Cost
$315,095
Indirect Cost
$113,111
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Mai, Tu H; Garland, Emily M; Diedrich, André et al. (2017) Hepatic and renal mechanisms underlying the osmopressor response. Auton Neurosci 203:58-66
Adefurin, A; Ghimire, L V; Kohli, U et al. (2017) Genetic variation in the alpha1B-adrenergic receptor and vascular response. Pharmacogenomics J 17:366-371
Kawai, V K; Levinson, R T; Adefurin, A et al. (2017) A genetic risk score that includes common type 2 diabetes risk variants is associated with gestational diabetes. Clin Endocrinol (Oxf) 87:149-155
Pezawas, Thomas; Diedrich, André; Robertson, David et al. (2017) Risk of arrhythmic death in ischemic heart disease: a prospective, controlled, observer-blind risk stratification over 10 years. Eur J Clin Invest 47:231-240
Kawai, Vivian K; Levinson, Rebecca T; Adefurin, Abiodun et al. (2017) Variation in the ?2A-adrenergic receptor gene and risk of gestational diabetes. Pharmacogenomics 18:1381-1386
Shaw, Brett H; Garland, Emily M; Black, Bonnie K et al. (2017) Optimal diagnostic thresholds for diagnosis of orthostatic hypotension with a 'sit-to-stand test'. J Hypertens 35:1019-1025
Arnold, Amy C; Garland, Emily M; Celedonio, Jorge E et al. (2017) Hyperinsulinemia and Insulin Resistance in Dopamine ?-Hydroxylase Deficiency. J Clin Endocrinol Metab 102:10-14
Kaufman, Melissa R; Chang-Kit, Laura; Raj, Satish R et al. (2017) Overactive bladder and autonomic dysfunction: Lower urinary tract symptoms in females with postural tachycardia syndrome. Neurourol Urodyn 36:610-613
Heusser, Karsten; Tank, Jens; Brinkmann, Julia et al. (2016) Preserved Autonomic Cardiovascular Regulation With Cardiac Pacemaker Inhibition: A Crossover Trial Using High-Fidelity Cardiovascular Phenotyping. J Am Heart Assoc 5:
Joy, Nino G; Mikeladze, Maia; Younk, Lisa M et al. (2016) Effects of equivalent sympathetic activation during hypoglycemia on endothelial function and pro-atherothrombotic balance in healthy individuals and obese standard treated type 2 diabetes. Metabolism 65:1695-1705

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