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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
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

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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