Comparative vasodilation of peroxynitrite and 3-morpholinosydnonimine.
Vasorelaxation mediated by peroxynitrite (ONOO-) and 3-morpholinosydnonimine (SIN-1) were investigated in isolated bovine intramammary arteries. Both ONOO- and SIN-1 relaxed U 46619-precontracted rings in a dose-dependent, endothelium-independent manner. Pretreatment with an adenylyl cyclase inhibitor, SQ 22536 [(9-tetrahydro-2-furyl)adenine], resulted in an enhanced ONOO--mediated relaxation, but did not modulate the response to SIN-1. ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), a potent and selective inhibitor of soluble guanylyl cyclase (sGC), did not significantly affect relaxant actions of ONOO-, but ODQ markedly attenuated SIN-1-elicited relaxation with a rightward shift in the dose-response curve and an unaltered maximal response. In the presence of carboxy-PTIO (2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide), a putative nitric oxide scavenger and ONOO- inactivator, the relaxant response to ONOO- was abolished, while relaxant actions of SIN-1 appeared to be unaffected. The results reveal a difference between ONOO- and SIN-1-mediated relaxation with regards to the role of the sGC and suggest that ONOO--evoked relaxation may not be associated with sGC activity, but rather depends on an sGC-independent mechanism triggered by ONOO- and/or NO itself. It also re-emphasizes that SIN-1 induces a vasorelaxant response, in part, via stimulation of sGC.
Trakranrungsie
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Department of Animal Health and Biomedical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 53706, USA.
Will
J A
JA
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects / Q000502:physiology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010069:Oxadiazoles / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001565:Benzoates; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007093:Imidazoles; C111257:NS 2028; D010069:Oxadiazoles; D010078:Oxazines; D016877:Oxidants; D014665:Vasodilator Agents; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D030421:Peroxynitrous Acid; C017759:9-(tetrahydro-2-furyl)-adenine; C002385:linsidomine; D008981:Molsidomine; D006162:Guanylate Cyclase; D000225:Adenine