Production of prostanoids and nitric oxide by infarcted heart in situ and the effect of aspirin.

The production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in infarcted and noninfarcted portions of the rabbit heart was studied prior to and following administration of acetylsalicylic acid (aspirin). Aspirin was administered intravenously (iv) as water-soluble Aspisol, d-lysinmono (acetylsalicylate) (Bayer, Leverkusen, Germany) into an ear vein. A branch of the left circumflex coronary artery was ligated. The animals were divided into three groups. The first group received 150 mg/kg/day of aspirin (75 mg/kg of aspirin every 12 h, n = 10). The first administration of aspirin was 1 h after ligation of the coronary artery and the last injection was 1 h before euthanasia. The second group received 5 mg/kg/day of aspirin (every 24 h, n = 10). A separate group of rabbits not receiving aspirin served as controls (n = 12). Two days following onset of ischemia, inducible form of nitric oxide synthase (iNOS) was measured in heart muscle and the oxidation products of nitric oxide (nitrite, NO-2 plus nitrate, NO-3: their sum referred to as NOx) were determined in arterial and coronary venous blood. Concentrations of both PGI2 and TXA2 were elevated in the infarcted portions of the heart compared to the noninfarcted regions. Formation of prostanoids was accompanied by increased activation of iNOS. Both doses of aspirin diminished the concentrations of PGI2 and TXA2 in infarcted heart muscle; in contrast, small doses of aspirin failed to influence myocardial iNOS activity. Apparently small doses of aspirin changed the relationship of iNOS to cyclooxygenase (COX). Coronary arterial-venous difference of NOx and myocardial iNOS activity showed parallel increases. Diminution of prostacyclin by aspirin can damage gastric mucosa and interfere with vasodilatation. Since NO counters these deficiencies, a combination of aspirin with a nitric oxide donor may be advantageous.