The purpose of the study is to explore the hypothesis that subsets of black patients with high blood pressure have one or more functional polymorphism of the 3 alpha adrenergic receptor (A2AR) genes and that combination of these mutations increase the overall prevalence of thrombotic stroke, hyperinsulinemia, hypertriglyceridemia, or salt sensitivity. The investigators plan to identify discrete subsets of black patients with essential hypertension compare them to well defined normotensives and determine if polymorphisms of the C10 and C2 A2AR genes are associated with a particular phenotypic expression in American blacks with and without hypertension. They have identified a polymorphism of the C10 A2AR gene which is associated with hypertension and a polymorphism in the C2AR gene associated with hyperinsulinemia. There are four specific aims. First to identify a discrete subset of black men and women with and without hypertension with polymorphisms of the A2AR genes encoded by chromosome 10 and 2. Second, to determine if specific polymorphisms of C10A2AR are associated with differences in the expression of platelet A2AR number, binding or aggregation; or decrease baroreceptor activity. Third to determine if polymorphisms of the chromosome 2 A2AR mediate hyperinsulinemia and adipocyte lipolysis in blacks. Finally to identify the A2AR encoding tissue-specific expression of the A2AR in the kidney and determine if genetic polymorphism of the receptor are associated with decreased natriuresis in black patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL050849-03
Application #
2415608
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1995-05-01
Project End
1999-04-30
Budget Start
1997-06-15
Budget End
1998-04-30
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Wayne State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Fox, W Christopher; Watson, Rex; Lockette, Warren (2006) Acute hypoxemia increases cardiovascular baroreceptor sensitivity in humans. Am J Hypertens 19:958-63
Finley Jr, J Clayton; O'Leary, Michael; Wester, Derin et al. (2004) A genetic polymorphism of the alpha2-adrenergic receptor increases autonomic responses to stress. J Appl Physiol 96:2231-9
Fox, W Christopher; Hall, Charlotte; Hall, Eric et al. (2003) Cardiovascular baroreceptors mediate susceptibility to hypothermia. Aviat Space Environ Med 74:132-7
Fox, W Chris; Lockette, Warren (2003) Unexpected syncope and death during intense physical training: evolving role of molecular genetics. Aviat Space Environ Med 74:1223-30
Vaitkevicius, Henrikas; Turner, Immanuel; Spalding, Aaron et al. (2002) Chloride increases adrenergic receptor-mediated platelet and vascular responses. Am J Hypertens 15:492-8
Vaitkevicius, Henrikas; Witt, Richard; Maasdam, Matthew et al. (2002) Ethnic differences in titratable acid excretion and bone mineralization. Med Sci Sports Exerc 34:295-302
MacKenzie, S; Vaitkevicius, H; Lockette, W (2001) Sequencing and characterization of the human thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene promoter. Biochem Biophys Res Commun 282:991-1000
Spalding, A; Vaitkevicius, H; Dill, S et al. (1998) Mechanism of epinephrine-induced platelet aggregation. Hypertension 31:603-7
Lockette, W; Kirkland, K; Farrow, S (1996) Alpha 2-adrenergic agonists increase cellular lactate efflux. Hypertension 27:1104-7
Freeman, K; Farrow, S; Schmaier, A et al. (1995) Genetic polymorphism of the alpha 2-adrenergic receptor is associated with increased platelet aggregation, baroreceptor sensitivity, and salt excretion in normotensive humans. Am J Hypertens 8:863-9