Effects of 12-HETE on isolated dog renal arcuate arteries.
12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) is one of the major noncyclooxygenase eicosanoids formed in vascular tissue. The vasoactive effects of the cytochrome P-450 product, 12(R)-HETE and the lipoxygenase product, 12(S)-HETE, on isolated, perfused renal arcuate arteries of the dog were investigated using videomicroscopy. R and S refer to stereoconfiguration of the hydroxy group at the twelfth position of this fatty acid structure. Cumulative doses of 12(R)-HETE produced a concentration-dependent vasoconstriction (n = 9) with a threshold dose of 10(-9) M. At a concentration of 3 x 10(-7) M, 12(R)-HETE reduced vascular diameter by 63 +/- 8 microns (from 306 +/- 17 microns), which was 37 +/- 6% of the maximal vasoconstrictor response to norepinephrine (10(-6) M). The effects of 12(R)-HETE were not altered by indomethacin (10(-6) M, n = 8). The vasoconstrictor response was associated with depolarization of vascular smooth muscle from -47 +/- 1 (15 cells) to -32 +/- 1 mV (12 cells). 12(S)-HETE was also a vasoconstrictor (n = 6), but the threshold concentration for vasoconstriction was 10(-8) M. Small renal arteries obtained from ischemic-injured, but not normal, kidneys produced a metabolite when incubated with arachidonic acid, which coeluted with a 12-HETE standard using reverse-phase high-pressure liquid chromatography. The rate of synthesis of this 12-HETE-like metabolite by renal arteries obtained from ischemic-injured and normal kidneys averaged 1.2 +/- 0.4 (n = 9) and 0.1 +/- 0.1 (n = 7) pmol.h-1.mg tissue-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Ma
Y H
YH
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Harder
D R
DR
Clark
J E
JE
Roman
R J
RJ
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001158:Arteries / Q000187:drug effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid