ACE inhibitors promote nitric oxide accumulation to modulate myocardial oxygen consumption

Background ACE inhibitors potentiate kinin-nitric oxide (NO)-dependent coronary vascular dilation, and NO can modulate myocardial oxygen consumption. Whether ACE inhibitors also affect myocardial O-2 consumption has not been established. Methods and Results Production of nitrite, a metabolite of NO in aqueous solution, in coronary microvessels and O-2 consumption in myocardium were quantified with the use of in vitro tissue preparations, the Greiss reaction, and a Clark-type O-2 electrode. In coronary microvessels, kininogen (the precursor of kinin; 10 mu g/mL) and three ACE inhibitors (captopril, enalaprilat. or ramiprilat; 10(-8) mol/L) increased nitrite production from 76+/-6 to 173+/-15, 123+/-2, 125+/-12, and 153+/-12 pmol/mg, respectively (all P<.05). In myocardium, kininogen (10 mu g/mL) and captopril, enalaprilat, or ramiprilat (10(-4) mol/L) reduced cardiac O-2 consumption by 41+/-2%, 19+/-3%, 25+/-2%, and 35+/-2%, respectively. The changes in both nitrite release and O-2 consumption in vitro were blocked by N-omega-nitro-L-arginine methyl eater or N-omega-nitro-L-arginine, inhibitors of endogenous NO formation. The effects were also blocked by HOE 140, which blocks the bradykinin B-2-kinin receptor, and serine protease inhibitors, which inhibit local kinin formation. Conclusions Our data indicate that stimulation of local kinin formation by use of a precursor for kinin formation or inhibition of kinin degradation by use of ACE inhibitors increases NO formation and is important in the control of cardiac O-2 consumption. Vasodilation and control of myocardial O-2 consumption by NO may contribute importantly to the therapeutic actions of ACE inhibitors in cardiac disease states.