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.
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.
|Kawai, Vivian K; Chung, Cecilia P; Solus, Joseph F et al. (2015) The ability of the 2013 American College of Cardiology/American Heart Association cardiovascular risk score to identify rheumatoid arthritis patients with high coronary artery calcification scores. Arthritis Rheumatol 67:381-5|
|Bestawros, Michael; Darbar, Dawood; Arain, Amir et al. (2015) Ictal asystole and ictal syncope: insights into clinical management. Circ Arrhythm Electrophysiol 8:159-64|
|Adefurin, A; Ghimire, L V; Kohli, U et al. (2015) Genetic variation in the ?1A-adrenergic receptor and phenylephrine-mediated venoconstriction. Pharmacogenomics J 15:310-5|
|Mar, Philip L; Raj, Vidya; Black, Bonnie K et al. (2014) Acute hemodynamic effects of a selective serotonin reuptake inhibitor in postural tachycardia syndrome: a randomized, crossover trial. J Psychopharmacol 28:155-61|
|Mai, Tu H; Wu, Jing; Diedrich, André et al. (2014) Calcitonin gene-related peptide (CGRP) in autonomic cardiovascular regulation and vascular structure. J Am Soc Hypertens 8:286-96|
|Gamboa, Alfredo; Okamoto, Luis E; Arnold, Amy C et al. (2014) Autonomic blockade improves insulin sensitivity in obese subjects. Hypertension 64:867-74|
|Ramirez, Claudia E; Okamoto, Luis E; Arnold, Amy C et al. (2014) Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. Hypertension 64:1235-40|
|Jeff, Janina M; Donahue, Brian S; Brown-Gentry, Kristin et al. (2014) Genetic variation in the *1-adrenergic receptor is associated with the risk of atrial fibrillation after cardiac surgery. Am Heart J 167:101-108.e1|
|Biaggioni, Italo (2014) New developments in the management of neurogenic orthostatic hypotension. Curr Cardiol Rep 16:542|
|Raj, Satish R (2014) Highlights in clinical autonomic neurosciences: Insights into the roles of the carotid body and carotid baroreceptor. Auton Neurosci 183:80-2|
Showing the most recent 10 out of 223 publications