The alpha-1 adrenergic receptors associated with vascular smooth muscle are one of the primary receptor classes used by the sympathetic nervous system to regulate systemic arterial blood pressure and blood flow. In this proposal, the investigators will use subtype specific antibodies to test the hypothesis that all known alpha-1 receptors are expressed on peripheral arteries. They will also characterize the distribution of these receptors along the arterial segment. Despite this wide expression, they hypothesize that the contractile activity of a particular blood vessel is modulated by only one dominant alpha-1 adrenergic receptor subtype, which may be different in different blood vessels. To test this hypothesis, antisense oligonucleotides directed against each of the known alpha-1 adrenergic receptor subtypes will be applied in vivo and the effect on smooth muscle contraction determined. They speculate that a better understanding of these receptors could lead to the development of newer, safer and more potent agents to treat hypertension and coronary artery disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL038120-08A1
Application #
2409104
Study Section
Special Emphasis Panel (ZRG4-HEM-2 (03))
Project Start
1987-04-01
Project End
2001-04-30
Budget Start
1998-05-08
Budget End
1999-04-30
Support Year
8
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Pharmacology
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506