ACE Inhibitors Promote Nitric Oxide Accumulation to Modulate Myocardial Oxygen Consumption

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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.