Effect of acetylsalicylic acid on nitric oxide production in infarcted heart in situ.

The effect of Acetylsalicylic Acid (ASA, Aspirin) on the myocardial production of the inducible form of nitric oxide synthase (iNOS) and the oxidation products of nitric oxide (nitrite, NO-2 and nitrate, NO-3: NOx) were studied in the rabbit heart two days after ligation of a branch of the left circumflex coronary artery. ASA was administered intravenously as AspisolR, DL-Lysinmono(acetylsalicylate) which is soluble in water. Animals received a total dose of 250, 375, or 500 mg/kg of ASA in five divided doses intravenously. Significant inhibition of iNOS was noted in the infarcted portion of the myocardium at 375 and 500 mg/kg of ASA. The reduction in myocardial nitric oxide (NO) production was paralleled by a diminution in coronary arterial-venous difference of NOx, demonstrating that ASA inhibition extended also to the oxidation products of NO. ASA is an inhibitor of cyclooxygenase (COX). The inhibition of iNOS by ASA demonstrates the close relationship between COX and iNOS activity in the heart in situ. Whether activity of the infarcted heart is influenced by the diminution in the production of NO by ASA is not known.