Differential Sensitivity among Nitric Oxide Donors toward ODQ-Mediated Inhibition of Vascular Relaxation

摘要: Nitric oxide (NO) donors are believed to exert their vasodilatory action through the activation of soluble guanylate cyclase (sGC), heme site which can be specifically inhibited by 1 H -[1,2,4]oxadiazolo[4,3- a ]quinoxalin-1-one (ODQ). We examined vascular relaxation rat aorta mediated eight different NO in presence ODQ (0.1, 1, or 10 μM), and demonstrated that these displayed sensitivities toward inhibition (ANOVA, P < .05). Among studied, S -nitrosothiols such as -nitroso- N -acetylpenicillamine (SNAP) -nitrosoglutathione exhibited partial resistance at 0.1 μM ODQ, whereas nitroglycerin (NTG) showed nearly complete this concentration ODQ. Three representing increasing sensitivity inhibition, SNAP sodium nitroprusside (SNP) NTG, were chosen for additional mechanistic studies. (1 μM) SNP, but not was partially reversed sulfhydryl donor, (100 phosphodiesterase inhibitor, zaprinast (10 specific cGMP. Our results strongly indicate mechanism(s) is identical each. In aorta, NTG appeared exhibit its effect exclusively sGC. On other hand, intact tissue, SNP could bring about vasodilation secondary pathway. These consistent with view induce additionally