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Vasodilator effects of organotransition-metal nitrosyl complexes, novel nitric oxide donors

TitleVasodilator effects of organotransition-metal nitrosyl complexes, novel nitric oxide donors
Publication TypeJournal Article
Year of Publication2000
AuthorsWang, YX, Legzdins, P, Poon, JS, Pang, CCY
JournalJournal of Cardiovascular Pharmacology
Volume35
Pagination73-77
Date PublishedJan
Type of ArticleArticle
ISBN Number0160-2446
KeywordsBLOOD, cyanide, ISOLATED TAIL ARTERY, metal-nitrosyl complexes, nitric oxide, nitroglycerin, nitrovasodilator, pressure, RAT AORTA, relaxation, RELEASE, sodium nitroprusside (SNP), SODIUM-NITROPRUSSIDE
Abstract

Nitrovasodilators cause endothelium-independent relaxation of blood vessels by generating nitric oxide (NO). We examined the relaxation and depressor effects of two organotransition-metal nitrosyl complexes, CpCr(NO)(2)Cl and CpMo(NO)(2)Cl, relative to those of the prototypal nitrovasodilators, nitroglycerin, and sodium nitroprusside (SNP), in phenylephrine-preconstricted aortic rings and conscious, unrestrained rats. CpCr(NO)(2)Cl, CpMo(NO)(2)Cl, nitroglycerin and SNP caused dose-dependent relaxation of aortic rings at maximal responses (E-max) of -118 +/- 4, -113 +/- 4, -104 +/- 1, and -128 +/- 5% and EC50 of 0.14 +/- 0.04, 22 +/- 4, 1.23 +/- 0.65, and 0.063 +/- 0.013 mu M, respectively. The dose-response curve of CpCr(NO)(2)Cl was displaced to the right by hemoglobin, as well as methylene blue, showing involvement of the NO/cGMP pathway. Unlike nitroglycerin, preexposure for 1 h to CpCr(NO)(2)Cl did not alter subsequent relaxation response to the compound, Intravenous bolus injections of CpCr(NO)(2)Cl, CpMo(NO)(2)Cl, nitroglycerin, and SNP caused dose-dependent decreases in MAP with E-max of -42 +/- 2, -51 +/- 8, -56 +/- 6, and -58 +/- 2 mm Hg and EC50 of 0.041 +/- 0.010, 13 +/- 4, 1.6 +/- 0.4, and 0.037 +/- 0.004 mu mol/kg, respectively. These results show that CpCr(NO)(2)Cl and CpMo(NO)(2)Cl are efficacious nitrovasodilators in vitro and in vivo.

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