Original ArticlesAmlodipine promotes kinin-mediated nitric oxide production in coronary microvessels of failing human hearts☆
Section snippets
Procurement of human hearts
Explanted hearts were harvested from 6 patients with end-stage cardiac failure during orthotopic cardiac transplantation and immediately placed in iced normal saline solution. The apical portion of each heart (which includes a portion of the left ventricular free wall, the septum, and the right ventricular free wall) was removed for this study. Within 30 minutes after removal, the hearts were transported on ice to our laboratory, where microvessels were isolated. The hearts were placed in iced
Effects of amlodipine on NO production by coronary microvessels in failing human hearts
Amlodipine (10−10 to 10−5 mol/L) caused a significant and dose-related increase in nitrite production in coronary microvessels of explanted failing human hearts (Figure 1). Compared with control, the highest dose of amlodipine increased nitrite release from 71 ± 4 to 126 ± 8 pmol/mg (p <0.01). Nitrite release induced by the highest dose of amlodipine was markedly reduced after pretreatment with L-NAME and HOE-140 (75 ± 5 and 84 ± 7 pmol/mg, respectively; all p <0.01, as compared with the
Discussion
Amlodipine can significantly increase NO production in the coronary microvessels of explanted failing human hearts. Compared with angiotensin-converting enzyme and neutral endopeptidase inhibitors, amlodipine induced a similar maximal NO production, indicating that amlodipine has a potent effect on coronary microvessels to release NO even after the development of severe congestive heart failure. It is therefore very likely that the difference between amlodipine and other calcium antagonists in
Conclusion
In summary, amlodipine significantly increased nitrite production in isolated coronary microvessels of explanted failing human hearts. This effect was blocked by L-NAME, HOE-140, and 3 serine protease inhibitors. These results suggest that amlodipine is a potent NO-releasing agent, as potent as ramiprilat and more potent than 2 neutral endopeptidase inhibitors. Amlodipine stimulates NO production from endothelium, most likely by promoting the effect of local kinins. Thus, amlodipine
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2022, Emergency Medicine Clinics of North AmericaCitation Excerpt :Amlodipine accounts for a disproportionate number of deaths related to overdose of cardiovascular drugs.1 Human and animal data suggest that amlodipine may also stimulate nitric oxide release, contributing additionally to vasodilation and potentially increased morbidity.24–27 Nondihydropyridines include verapamil and diltiazem.
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2005, American Journal of MedicineCitation Excerpt :Laboratory studies have demonstrated that amlodipine has beneficial effects on endothelial dysfunction.42–44 One early investigation recorded the effects on human arterial vessels with the administration of different antihypertensive agents, including an ACE inhibitor and a calcium channel blocker.43 The aim of this study was to determine the effect of amlodipine on NO production in failing human hearts along with the role of kinins.
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These studies were supported by grants PO-1-HL 43023, HL 50142, HL 18579#, and HL 53053 from the National Heart, Lung, and Blood Institute and by Fellowship 96-103 (XZ) from the New York Affiliate of the American Heart Association.