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.
|Porter, J E; Edelmann, S E; Waugh, D J et al. (1998) The agonism and synergistic potentiation of weak partial agonists by triethylamine in alpha 1-adrenergic receptor activation: evidence for a salt bridge as the initiating process. Mol Pharmacol 53:766-71|