(Circulation. 1997;95:176-182.)
© 1997 American Heart Association, Inc.
Articles |
ACE Inhibitors Promote Nitric Oxide Accumulation to Modulate Myocardial Oxygen Consumption
the Departments of Physiology and Pharmacology (A.N.), New York Medical College, Valhalla.
Correspondence to Thomas H. Hintze, PhD, Professor, Department of Physiology, New York Medical College, Valhalla, NY 10595.
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 O2 consumption has not been established.
Methods and Results Production of nitrite, a metabolite of NO in aqueous solution, in coronary microvessels and O2 consumption in myocardium were quantified with the use of in vitro tissue preparations, the Greiss reaction, and a Clark-type O2 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 O2 consumption by 41±2%, 19±3%, 25±2%, and 35±2%, respectively. The changes in both nitrite release and O2 consumption in vitro were blocked by N
-nitro-L-arginine methyl ester or N-nitro-L-arginine, inhibitors of endogenous NO formation. The effects were also blocked by HOE 140, which blocks the bradykinin B2-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 O2 consumption. Vasodilation and control of myocardial O2 consumption by NO may contribute importantly to the therapeutic actions of ACE inhibitors in cardiac disease states.
Key Words: endothelium-derived factors • oxygen • enzymes
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