ACE Inhibitors Promote Nitric Oxide Accumulation to Modulate Myocardial Oxygen Consumption

Abstract

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 μg/mL) and three ACE inhibitors (captopril, enalaprilat, or ramiprilat; 10 −8 mol/L) increased nitrite production from 76±6 to 173±15, 123±12, 125±12, and 153±12 pmol/mg, respectively (all P <.05). In myocardium, kininogen (10 μg/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 ω -nitro- l -arginine methyl ester or N ω -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.