The overall hypothesis to be tested in this proposal is that increases in production of lipoxygenase metabolites and decreases in production of epoxygenase metabolites contribute to enhanced vascular tone of preglomerular vessels and elevation in blood pressure associated with increased circulating levels of angiotensin II. Rats will be prepared with chronic infusion of angiotensin II and the development of hypertension followed. At selected time intervals, the metabolites of epoxygenase and lipoxygenase will be measured. The reactivity of renal microvasculatures will be evaluated and assayed for the production of the various metabolites of arachidonic acid. In addition, in vitro juxtamedullary nephron techniques combined with video microscopy will be used to determine preglomerular vascular tone in vitro; the various contributions of metabolites lipoxygenase and epoxygenase will be assessed using pharmacological inhibition of these probes both in the acute and chronic situation. Results of these studies will further define the renin-angiotensin system and determine the role of arachidonic acid metabolism in the development of angiotensin-dependent hypertension.

R29HL059699

1998-01-01

2001-12-31