The long term goal of the proposal is to develop anti-hypertension drugs based on the premise that a distinct form of the parathyroid Ca2+ receptor (CaR) exists in perivascular nerves and that stimulation of this receptor leads to elaboration of a vasodilator substance. Preliminary data indicate that the CaR may be a sensory that is involved in the regulation of blood pressure. The applicant advances several lines of evidence to support his hypothesis that the CaR may be a key element in modulating vascular tone. In aim 1, a hypothesis will be tested which states that chronic or acute perivascular denervation results in reduction in perivascular CaR expression and a reduction in extracellular Ca2+ induced vascular tone. In such studies, denervation will be induced by two means and physiological methods, employed routinely by the applicant, will be used to study alterations in vascular tone. In aim 2, the interesting observation of an apparent change in splicing of the parathyroid calcium receptor in nerve will be investigated by 5'-RACE, cDNA cloning, and cDNA expression. PROPOSED COMMERCIAL APPLICATION: The goal and associated commercial application of this grant is to determine the feasibility of using the perivascular sensory nerve Ca2+ receptor as a target for the design of drugs that can be used as antihypertensive vasodilators with increased efficacy for salt sensitive hypertensive patients, including aged and minority populations.
Thesaurus Terms: antihypertensive agent, calcium ion, receptor, receptor expression, vascular smooth muscle nervous control, vasodilator RNA splicing, blood pressure, cardiovascular pharmacology, parathyroid gland denervation, laboratory rat, molecular cloning, tissue /cell culture
