Oxidation Products of Nitric Oxide, NO2and NO3, in Plasma after Experimental Myocardial Infarction

Nitrite and nitrate (NO2and NO3), the oxidative products of nitric oxide (NO), were elevated in the plasma of rabbits on the third day following ligation of a coronary artery. This elevation coincided with increased activity of the inducible form of nitric oxide synthase (iNOS) in infarcted heart muscle. Data are reported which relate the elevated plasma concentrations of NO2+NO3(NOx) to the increased induction of iNOS in an infarcted heart. NO2and NO3in plasma were measured by chemiluminescence. Nitrate was converted to nitrite by nitrate reductase. Plasma from the ear vein, right and left ventricle, and coronary sinus were analyzed for NOx, and iNOS activity was enzymatically determined in infarcted, risk, and normal areas of the heart. The production equivalent of NOxby the heart and lung was also calculated. In addition, the effect of a specific inhibitor of iNOS, S-methylisothiourea sulfate (SMT) on plasma concentration and myocardial production of NOxwas determined. It was concluded that the elevation of plasma NOxfollowing onset of myocardial ischemia was directly related to increased induction of iNOS in the heart. This conclusion was based on a proportional and simultaneous increase in NOxplasma concentration with myocardial iNOS activation. The inhibitory effect of SMT furnished additional confirmation of the relationship between myocardial iNOS activation and NOxplasma levels in experimental myocardial infarction.