Inhibition of renal vascular 20-HETE production impairs autoregulation of renal blood flow.
The present study evaluated the role of endogenous P-450 metabolites of arachidonic acid (AA) on autoregulation of renal blood flow in rats. Whole kidney and cortical blood flows were well autoregulated when renal perfusion pressure was varied from 150 to 100 mmHg. Infusion of 17-octadecynoic acid (17-ODYA) into the renal artery (33 nmol/min) increased cortical and papillary blood flows by 12.6 +/- 2.5 and 26.5 +/- 4.6%, respectively. After 17-ODYA, autoregulation of whole kidney and cortical blood flows was impaired. Intrarenal infusion of miconazole (8 nmol/min) had no effect on autoregulation of whole kidney, cortical, or papillary blood flows. 17-ODYA (1 microM) inhibited the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) and 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) by renal preglomerular microvessels in vitro by 83.7 +/- 7.4% and 89.0 +/- 4.9%, respectively. Miconazole (1 microM) reduced the formation of EETs by 86.4 +/- 5.7%, but it had no effect on the production of 20-HETE. These results suggest that endogenous P-450 metabolites of AA, particularly 20-HETE, may participate in the autoregulation of renal blood flow.
Zou
A P
AP
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Imig
J D
JD
Kaldunski
M
M
Ortiz de Montellano
P R
PR
Sui
Z
Z
Roman
R J
RJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006706:Homeostasis; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D007672:Kidney Cortex / Q000098:blood supply*; D007679:Kidney Medulla / Q000098:blood supply; D007700:Kinetics; D008297:Male; D008825:Miconazole / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*
D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; C047008:17-octadecynoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D008825:Miconazole; D003577:Cytochrome P-450 Enzyme System