EFFECTS OF INTRARENAL INFUSION OF 17-OCTADECYNOIC ACID ON RENAL ANTIHYPERTENSIVE MECHANISMS IN ANESTHETIZED RABBITS

To characterize the role of cytochrome P450 metabolism of fatty acids in the renal response to increased renal perfusion pressure, we tested the effects of renal arterial infusion of 17-octadecynoic acid (17-OD YA, 450 nmol/min) on renal and systemic hemodynamic, and renal excreto ry responses to step-wise increases in renal perfusion pressure (RPP) in anesthetized rabbits, using an extracorporeal circuit for renal aut operfusion. Inhibition of cytochrome P450-dependent fatty acid metabol ism was estimated by comparing the metabolism of arachidonic acid in m icrosomes prepared from the kidneys of control and 17-ODYA-treated ani mals. Step-wise increases in RPP decreased mean arterial pressure, whi ch previous studies have indicated is attributable to the release of a depressor hormone from the renal medulla. Elevations in RPP also incr eased renal blood now and glomerular filtration rate, and the absolute and fractional excretions of urine and sodium. Intrarenal infusion of 17-ODYA reduced the metabolism of arachidonic acid to 20-hydroxyeicos atetraenoic acid by 41%, but it did not significantly influence the re sponses to increased renal perfusion pressure. We conclude that either the responses elicited by increased renal perfusion pressure in anest hetized rabbits do not depend on cytochrome P450-dependent fatty acid metabolism, or that cytochrome P450 activity must be inhibited by more than was achieved in the present study (41%), before functional effec ts on the response to increased renal perfusion pressure are observed, Am J Hypertens 1998;11:803-812 (C) 1998 American Journal of Hypertens ion, Ltd.