Vascular smooth muscle relaxation mediated by nitric oxide donors: a comparison with acetylcholine, nitric oxide and nitroxyl ion

I Vasorelaxant properties of three nitric oxide (NO) donor drugs (glyceryl trinitrate, sodium nitroprusside and spermine NONOate) in mouse aorta (phen ylephrine pre-contracted) were compared with those of endothelium-derived N O (generated with acetylcholine), NO free radical (NO; NO gas solution) and nitroxyl ion (NO-; from Angeli's salt). 2 The soluble guanylate cyclase inhibitor, ODQ (1H-(1,2,4-)oxadiazolo(4,3-a )-quinoxalin-1-one; 0.3, 1 and 10 muM), concentration-dependently inhibited responses to all agents. 10 muM ODQ abolished responses to acetylcholine a nd glyceryl trinitrate, almost abolished responses to sodium nitroprusside but produced parallel shifts (to a higher concentration range; no depressio n in maxima) in the concentration-response curves for NO gas solution, Ange li's salt and spermine NONOate. 3 The NO scavengers, carboxy-PTIO, (2-(4-carboxyphenyl)-4,4,5,5-tetramethyl -indazoline-1-oxyl-3-oxide; 100 muM) and hydroxocobalamin (100 muM), both i nhibited responses to NO gas solution and to the three NO donor drugs, but not Angeli's salt. Hydroxocobalamin, but not carboxy-PTIO, also inhibited r esponses to acetylcholine. 4 The NO- inhibitor, L-cysteine (3 mm), inhibited responses to Angeli's sal t, acetylcholine and the three NO donor drugs, but not NO gas solution. 5 The data suggest that, in mouse aorta, responses to all three NO donors i nvolve (i) activation of soluble guanylate cyclase, but to differing degree s and (ii) generation of both NO and NO-. Glyceryl trinitrate and sodium ni troprusside, which generate NO following tissue bioactivation, have profile s resembling the profile of endothelium-derived NO more than that of exogen ous NO. Spermine NONOate, which generates NO spontaneously outside the tiss ue, was the drug that most closely resembled (but was not identical to) exo genous NO.