Amlodipine promotes kinin-mediated nitric oxide production in coronary microvessels of failing human hearts

Xiaoping Zhang, Maryanne R. Kichuk, Seema Mital, Mehmet Oz, Robert Michler, Alberto Nasjletti, Gabor Kaley, Thomas H. Hintze

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Recently, we found that amlodipine can release nitric oxide (NO) from canine coronary microvessels, which raises the question of whether amlodipine can also promote coronary NO production in failing human hearts. The goal of this study was to define the effect of amlodipine on NO production in failing human hearts and to determine the role of kinins in the control of NO production induced by amlodipine. Six explanted human hearts with end-stage heart failure were obtained immediately at transplant surgery. Coronary microvessels were isolated as previously described, and nitrite, the stable metabolite of NO in aqueous solution, was measured using the Griess Reaction. Amlodipine (10-10 to 10-5 mol/L) significantly increased nitrite production in coronary microvessels in a dose-dependent manner. The increase in nitrite in response to the highest dose of amlodipine (79%) was similar in magnitude to either that of the angiotensin-converting enzyme inhibitor ramiprilat (74%) or the neutral endopeptidase inhibitors phosphoramidon (61%) and thiorphan (72%). Interestingly, the increase in nitrite production induced by amlodipine was entirely abolished by N(ω)-nitro-L-arginine methyl ester and also HOE-140 (a bradykinin-2 antagonist) and dichloroisocoumarin (a serine protease inhibitor that blocks kallikrein activity). These results indicate that amlodipine can promote coronary NO production in failing human hearts and that this effect is dependent on a kinin-mediated mechanism. Copyright (C) 1999 Excerpta Medica Inc.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalAmerican Journal of Cardiology
Volume84
Issue number4 SUPPL. 1
DOIs
StatePublished - Aug 19 1999

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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