Role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip hypertension

Objective: To examine the role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip (1-K, 1C) hypertension in rats. Design: The stimulus for the release of an antihypertensive lipid from the kidney is not known. This study examined whether cortical or papillary blood flow is altered after removal of the clip from the renal artery of 1 -K, 1 C hypertensive rats, and the effects of blockade of the renal metabolism of arachidonic acid by P-450 with 1 7-octadecynoic acid (17-ODYA) on the fall in blood pressure. Methods: Cortical and medullary blood flows were measured using laser-Doppler flowmetry. 17-ODYA (33nmol/min) was infused directly into the renal artery to examine the effect of inhibition of renal P-450 activity on reversal of 1-K, 1C hypertension. The renal metabolism of arachidonic acid in control and in 1-K, 1C hypertensive rats was assessed by incubating microsomes with [¹⁴C]-arachidonic acid, the metabolites formed being measured using reverse-phase high-performance liquid chromatography. The antihypertensive effects of these P-450 metabolites of arachidonic acid were compared with those of medullipin I after intravenous administration in conscious spontaneously hypertensive rats (SHR). Results: Cortical and papillary blood flow increased significantly and arterial pressure fell after unclipping the renal artery in the 1-K, 1C hypertensive rats. 17-ODYA prevented the fall in blood pressure after unclipping. The production of epoxy- and dihydroxy-eicosatrienoic acids was elevated in microsomes prepared from the renal cortex of the 1-K, 1C hypertensive rats. However, intravenous administration of these metabolites did not mimic the effect of medullipin I to lower arterial pressure in SHR. Conclusion: Elevations in renal cortical or papillary blood flow, or both, may stimulate the release of a P-450-derived antihypertensive lipid from the kidney after unclipping of the renal artery in 1-K, 1C hypertensive rats. However, it is unlikely that this substance is a P-450 metabolite of arachidonic acid.