Inhibition of nitrergic relaxations by a selective inhibitor of the soluble guanylate cyclase

Abstract

1. The actions of 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1 (ODQ), a specific inhibitor of the soluble guanylate cyclase (SGC), were investigated in the rabbit anococcygeus muscle. 2. ODQ (1 nM-1 μM) inhibited in a concentration-dependent manner the relaxations induced by electrical held stimulation (EFS; 50 V, 0.3 ms duration, 1 Hz, for 5 s, every 120 s). 3. ODQ (1 μM) also inhibited the relaxations elicited by EFS (50 V, 0.3 ms duration, 1, 2.5, 5, 10 Hz, for 5 s) and sodium nitroprusside (SNP; 1 μM) without affecting those induced by isoprenaline (1 μM), atrial natriuretic peptide (ANP; 100 nM) or an analogue of cyclic GMP (8-pCPT-cyclic GMP; 500 μM). 4. ODQ (1 μM) inhibited the elevations in the concentration of cyclic GMP induced by SNP or EFS, but not by ANP. ODQ did not affect the concentrations of cyclic AMP. 5. Nitrergic relaxation in this tissue appears, therefore, to be mediated via activation of SGC.