Nitric oxide/nucleophile complexes: a unique class of nitric oxide-based vasodilators.
Complexes of nitric oxide (NO) with nucleophiles, also known as nitric oxide/nucleophile adducts or NONOates, appear to offer many advantages as research tools in cardiovascular pharmacology and may have future clinical potential as well. A wide variety of NONOates can be synthesized simply by exposing various nucleophilic compounds to NO. The products are generally stable as solids and highly soluble in aqueous media. The potent vasodilator activity displayed by select members of this series is endothelium independent and is mediated by the free NO that is released on dissolution, which activates smooth-muscle guanylate cyclase with subsequent intracellular cyclic guanosine monophosphate production. NO release from the NONOate complexes is not catalyzed by exogenous thiol or albumin. The NONOates differ from other currently available nitrovasodilators in that their potency as vasorelaxants correlates closely with data on their first-order rates of spontaneous reversion to NO in simple aqueous buffers. The compounds' properties can be conveniently altered by changing the identity of the nucleophilic residue. Continued work with NONOate complexes may provide useful clinical agents as well as improved tools for probing the bioregulatory roles of NO.
Morley
D
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Division of Cardiovascular Diseases, Hahnemann University, Philadelphia, Pennsylvania 19102-1192.
Keefer
L K
LK
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D014665:Vasodilator Agents; D009569:Nitric Oxide