Mechanism of hydroxyl radical-induced modulation of vascular tone.
We investigated the effects of hydroxyl radicals (OH) generated by a .OH-generating system (dihydroxyfumarate [DHF], adenosine diphosphate [ADP], and FeCl3) on isolated rabbit aorta suspended in Krebs-Ringer solution. The .OH-generating system produced a concentration-dependent generation of .OH. .OH relaxed rabbit aorta and norepinephrine (NE)-precontracted aorta in a concentration-dependent manner. Mannitol completely prevented this relaxation. Relaxation was completely absent in preparations denuded of endothelium. The relaxant effect was reduced by 62% by an inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine), by 58% by an inhibitor of guanylate cyclase (methylene blue), by 48% by an inhibitor of cyclooxygenase (indomethacin), and by 83% by an adenosine triphosphate (ATP)-sensitive K+ channel blocker (glyburide). The inhibition of .OH-induced relaxation by a combination of indomethacin, methylene blue, and glyburide was not greater than by each of the individual agents. These results indicate that .OH produces a relaxation of the aorta that is completely endothelium-dependent and is partly mediated by an endothelium-derived relaxing factor (nitric oxide), vasodilatory arachidonic acid metabolites, and an ATP-sensitive K+ channel.
Bharadwaj
L A
LA
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Prasad
K
K
D000818:Animals; D001011:Aorta; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D017665:Hydroxyl Radical; D008353:Mannitol; D019001:Nitric Oxide Synthase; D005905:Glyburide; D008751:Methylene Blue; D009638:Norepinephrine; D007213:Indomethacin