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 perfusion pressure and on autoregulation of glomerular capillary pressure using the rat juxtamedullary nephron microvascular preparation perfused in vitro with a cell-free perfusate containing 5% albumin. The basal diameters of the proximal and distal afferent arterioles averaged 28 +/- 1 (n = 32) and 18 +/- 1 micron (n = 23), respectively, at a control perfusion pressure of 80 mmHg. The diameters of these vessels decreased by 8% when perfusion pressure was elevated from 80 to 160 mmHg. After addition of cytochrome P-450 inhibitors (either 17-octadecynoic acid, 20 microM; 7-ethoxyresorufin, 10 microM; or miconazole, 20 microM) to the perfusate, the diameters of the proximal and distal afferent arterioles increased by 6% in response to the same elevation in perfusion pressure. 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. Autoregulation of glomerular capillary pressure was impaired after addition of the cytochrome P-450 inhibitors, and it increased by 18 +/- 2 mmHg when perfusion pressure was varied over the same range. These results indicate that cytochrome P-450 inhibitors attenuate the vasoconstrictor response of afferent arterioles to elevations in renal perfusion pressure and impair autoregulation of glomerular capillary pressure, suggesting a possible role for cytochrome P-450 metabolites of arachidonic acid in these responses.
Imig
J D
JD
Department of Physiology, Medical College of Wisconsin, Milwaukee.
Zou
A P
AP
Ortiz de Montellano
P R
PR
Sui
Z
Z
Roman
R J
RJ
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D007672:Kidney Cortex / Q000378:metabolism*; D008825:Miconazole / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010078:Oxazines / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology
D065607:Cytochrome P-450 Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D010078:Oxazines; D016718:Arachidonic Acid; C047008:17-octadecynoic acid; C007649:ethoxyresorufin; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D008825:Miconazole; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid