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Impaired vasodilatation response to amrinone in the forearm of patients with congestive heart failure: role of endothelium-derived nitric oxide.

Abstract：

:Recent in vitro experiments have shown that amrinone enhances the release of nitric oxide (NO) from the endothelium and induces NO mediated vasodilatation. This in vivo study examined whether amrinone causes vasodilatation mediated by endothelium-derived NO, and whether this effect is attenuated in patients with endothelial dysfunction. Eight patients with congestive heart failure and 10 age- and sex-matched healthy volunteers were studied. Forearm blood flow (FBF) was measured before and during infusion of drugs of acetylcholine, amrinone, and nitroglycerin in incremental doses. After the completion of these measurements, 100 micromol of N(G)-monomethyl-L-arginine (L-NMMA) was infused intraarterially. Thereafter, FBF measurement in response to incremental doses of amrinone was repeated. Infusion of incremental doses of amrinone caused a comparable increase in amrinone plasma concentration in both groups. Baseline FBF was 3.2+/-0.79 ml/min/100 ml in controls vs. 2.91+/-0.79 ml/min/100 ml in patients (p = 0.43). In both groups, FBF increased in response to acetylcholine, amrinone, and nitroglycerin. During infusion of the highest dose of nitroglycerin, FBF was not different between the two groups (p = 0.51); however, FBF during infusion of the highest doses of acetylcholine and amrinone was significantly less in patients than in controls: 9.75+/-2.69 vs. 24.87+/-8.65 ml/min/100 ml (p < 0.001) and 3.79+/-1.21 vs. 7.15+/-2.06 ml/min/100 ml (p < 0.001), respectively. L-NMMA significantly depressed the increase in FBF in response to amrinone in controls, but not in patients. In conclusion, the selective PDE III inhibitor, amrinone, has endothelium-derived NO-mediated vasodilating effects in addition to direct effects. This property may be impaired in patients with endothelial dysfunction.

journal_name

J Cardiovasc Pharmacol

journal_title

Journal of cardiovascular pharmacology

authors

Sakane T,Ishibashi Y,Shimada T,Takahashi N,Sugamori T,Hirano Y,Ohata S,Inoue SI,Nakamura K,Murakami Y

doi

10.1097/00005344-200008000-00008

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

188-95

issue

eissn

0160-2446

issn

1533-4023

journal_volume

pub_type

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Impaired vasodilatation response to amrinone in the forearm of patients with congestive heart failure: role of endothelium-derived nitric oxide.