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Vascular smooth muscle relaxation mediated by nitric oxide donors: a comparison with acetylcholine, nitric oxide andnitroxyl ion
Author(s) -
Wanstall Janet C,
Jeffery Trina K,
Gambino Agatha,
Lovren Fina,
Triggle Christopher R
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704269
Subject(s) - chemistry , sodium nitroprusside , nitric oxide , acetylcholine , hydroxocobalamin , phenylephrine , pharmacology , endothelium derived relaxing factor , soluble guanylyl cyclase , vasodilation , spermine , vascular smooth muscle , biochemistry , endocrinology , blood pressure , cyclic gmp , smooth muscle , enzyme , organic chemistry , medicine , cyanocobalamin , vitamin b12
Vasorelaxant properties of three nitric oxide (NO) donor drugs (glyceryl trinitrate, sodium nitroprusside and spermine NONOate) in mouse aorta (phenylephrine pre‐contracted) were compared with those of endothelium‐derived NO (generated with acetylcholine), NO free radical (NO · ; NO gas solution) and nitroxyl ion (NO − ; from Angeli's salt). The soluble guanylate cyclase inhibitor, ODQ (1 H ‐(1,2,4‐)oxadiazolo(4,3‐ a )‐quinoxalin‐1‐one; 0.3, 1 and 10 μ M ), concentration‐dependently inhibited responses to all agents. 10 μ M ODQ abolished responses to acetylcholine and glyceryl trinitrate, almost abolished responses to sodium nitroprusside but produced parallel shifts (to a higher concentration range; no depression in maxima) in the concentration‐response curves for NO gas solution, Angeli's salt and spermine NONOate. The NO · scavengers, carboxy‐PTIO, (2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethyl‐imidazoline‐1‐oxyl‐3‐oxide; 100 μ M ) and hydroxocobalamin (100 μ M ), both inhibited responses to NO gas solution and to the three NO donor drugs, but not Angeli's salt. Hydroxocobalamin, but not carboxy‐PTIO, also inhibited responses to acetylcholine. The NO − inhibitor, L‐cysteine (3 m M ), inhibited responses to Angeli's salt, acetylcholine and the three NO donor drugs, but not NO gas solution. The data suggest that, in mouse aorta, responses to all three NO donors involve (i) activation of soluble guanylate cyclase, but to differing degrees and (ii) generation of both NO · and NO − . Glyceryl trinitrate and sodium nitroprusside, which generate NO following tissue bioactivation, have profiles resembling the profile of endothelium‐derived NO more than that of exogenous NO. Spermine NONOate, which generates NO spontaneously outside the tissue, was the drug that most closely resembled (but was not identical to) exogenous NO.British Journal of Pharmacology (2001) 134 , 463–472; doi: 10.1038/sj.bjp.0704269