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

Recent in vitro experiments have shown that amrinone enhances the release o f nitric oxide (NO) from the endothelium and induces NO mediated vasodilata tion. This in vivo study examined whether amrinone causes vasodilatation me diated 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. Forea rm blood flow (FBF) was measured before and during infusion of drugs of ace tylcholine, amrinone, and nitroglycerin in incremental doses. After the com pletion of these measurements, 100 mu mol of N-O-monomethyl-L-arginine (L-N MMA) was infused intraarterially. Thereafter, FBF measurement in response t o 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 mi in patients (p = 0.43). In both groups, FBF in creased in response to acetylcholine, amrinone, and nitroglycerin. During i nfusion of the highest dose of nitroglycerin, FBF was not different between the two groups (p = 0.51); however, FBF during infusion of the highest dos es 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 mi (p < 0.001), respectively. L-N MMA significantly depressed the increase in FBF in response to amrinone in controls, but not in patients. In conclusion, the selective PDE III inhibit or, amrinone, has endothelium-derived NO-mediated vasodilating effects in a ddition to direct effects. This property may be impaired in patients with e ndothelial dysfunction.