The autonomic nervous system is the crucial link between the brain and the cardiovascular system. It is the final common pathway by which central disturbances - whether initiated by exogenous psychological or physical stress, or endogenous biochemical or structural perturbation - are translated into alterations in cardiac, endocrine, and vascular function. There is compelling evidence that disordered autonomic engagement of the heart and vasculature contributes importantly to many forms of cardiovascular disease: arrhythmias, hypertension, syncope, stroke, myocardial infarction, and sudden death. The goal of this Program Project is to achieve better understanding of how the brain exerts control over the autonomic nervous system. The integrating of the grant is autonomic cardiovascular regulation and the means by which the autonomic nervous system controls effector tissues. The rationale of the Program Project is the tightly coordinated testing of hypotheses addressing autonomic modulation of cardiovascular function in health and disease. Component projects address central and peripheral autonomic mechanisms, employing both integrated and reductionist approaches. The roles of specific body constituents (insulin, hormones, adrenoreceptors), endogenous mediators (nitric oxide, water), and afferent (osmopressor response), efferent (obesity hypertension), and endocrine (hypoglycemia, exercise, and hyperglycemia) mechanisms are examined. The programmatic approach facilitates the bidirectional transfer of information between the laboratory and the clinic because it brings together investigators with a wide range of skills who have a track record of discovering new fundamental knowledge and applying it to the creation of practical improvements in human health. This Program Project should lead directly to improved therapy in cardiovascular disease.

Public Health Relevance

The brain and nervous system control blood pressure and how the body handles sugar (glucose). The research we propose includes a team of scientists working together to find better ways to control autonomic regulation of glucose and blood pressure. With better ways to control blood pressure and blood sugar, we can improve we will be able to improve the health of many people with these diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL056693-16
Application #
8268649
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Maric-Bilkan, Christine
Project Start
1998-08-01
Project End
2017-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
16
Fiscal Year
2012
Total Cost
$1,831,351
Indirect Cost
$555,307
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
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

Showing the most recent 10 out of 309 publications