The effect of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and charybdotoxin (CTX) on relaxations of isolated cerebral arteries to nitric oxide.

摘要: The mechanism underlying smooth muscle relaxations of cerebral arteries in response to nitric oxide is still not completely understood. present study was designed determine the role soluble guanylate cyclase a oxide/nucleophile complex, diethylaminodiazen-1-ium-1,2-dioate (DEA-NONOate). Rings canine middle without endothelium were suspended Krebs-Ringer bicarbonate solution for isometric tension recording. levels guanosine 3',5'-cyclic monophosphate (cyclic GMP) measured by radioimmunoassay technique. During contractions uridine 5'-triphosphate (UTP), DEA-NONOate (10(-10) 10(-5) M) caused concentration-dependent relaxations. Measurements cyclic GMP arterial wall demonstrated that potent stimulator and subsequent formation GMP. Increasing concentrations selective inhibitor, 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), reduction both production DEA-NONOate. Interestingly, presence highest concentration (3 x 10(-6) ODQ, M abolished, whereas same almost complete relaxation, suggesting mechanisms independent may mediate relaxing effect high donor. A Ca2+-activated potassium channel blocker charybdotoxin (CTX) significantly reduced resistant supporting idea activate channels independently results our suggest under physiological conditions, key mediator oxide. However, pathological conditions associated with induction synthase increased biosynthesis (e.g., ischemia, inflammation, sepsis), other than be activated.