CYTOCHROME-P-450 INHIBITORS ALTER AFFERENT ARTERIOLAR RESPONSES TO ELEVATIONS IN PRESSURE

The present study evaluated the effects of cytochrome P-450 inhibitors on the response of the renal microvasculature to changes in renal per fusion pressure and on autoregulation of glomerular capillary pressure using the rat juxtamedullary nephron microvascular preparation perfus ed in vitro with a cell-free perfusate containing 5% albumin. The basa l diameters of the proximal and distal afferent arterioles averaged 28 +/- 1 (n = 32) and 18 +/- 1 mu m (n = 23), respectively, at a control perfusion pressure of 80 mmHg. The diameters of these Vessels decreas ed by 8% when perfusion pressure was elevated from 80 to 160 mmHg. Aft er addition of cytochrome P-450 inhibitors (either 17-octadecynoic aci d, 20 mu M; 7-ethoxyresorufin, 10 mu M; or miconazole, 20 mu M) to the perfusate, the diameters of the proximal and distal afferent arteriol es increased by 6% in response to the same elevation in perfusion pres sure. Control glomerular capillary pressure averaged 43 +/- 1 mmHg (n = 32) at a renal perfusion pressure of 80 mmHg and increased by only 9 +/- 1 mmHg when perfusion pressure was elevated to 160 mmHg. Autoregu lation of glomerular capillary pressure was impaired after addition of the cytochrome P-450 inhibitors, and it increased by 18 +/- 2 mmHg wh en perfusion pressure was varied over the same range. These results in dicate that cytochrome P-450 inhibitors attenuate the vasoconstrictor response of afferent arterioles to elevations in renal perfusion press ure and impair autoregulation of glomerular capillary pressure, sugges ting a possible role for cytochrome P-450 metabolites of arachidonic a cid in these responses.