Superoxide and nitroglycerin stimulate release of PGF(2 alpha) and TxA(2) in isolated rat heart

The aim of this study was to investigate the effects of nitroglycerin (NTG), a nitric oxide (NO) donor used as a vasodilating agent, on prostanoid [e.g., prostaglandin (PG)] release in the O-2(-)-pretreated rat heart. Perfusion of O-2(-), generated by a xanthine oxidase-purine coupling, caused elevation (P < 0.05) of the coronary perfusion pressure (CPP) after 20 min (from 57.1 +/- 3.9 during the control period to 72.2 +/- 3.9 mmHg, P < 0.05). O-2(-) caused increased release of PGF(2 alpha) from 3.6 +/- 0.7 to 20.6 +/- 4.4 pmol . min(-1) . g(-1) and of thromboxane A(2)(TxA(2)) from 2.4 +/- 0.4 to 9.6 +/- 1.6 pmol . min(-1) . g(-1) (P < 0.001) with no significant changes in PGE(2) and PGI(2) release, During the 20-min washout of O-2(-) from the heart with normal Krebs solution, release of PGF(2 alpha) and TxA(2) decreased to 8.7 +/- 1.4 and 6.3 +/- 1.7 pmol . min(-1) . g(-1), respectively, and the release of PGE(2) and PGI(2) markedly increased from 11.1 +/- 2.9 to 25.4 +/- 3.6 and 157.2 +/- 16.4 to 413.2 +/- 41.4 pmol . min(-1) . g(-1), respec tively (P < 0.05), without lowering the elevated CPP Administration of 4 mu M NTG during the washout period paradoxically augmented the elevated CPP to 133.3 +/- 0.6% and was associated with a doubling (P < 0.05) of PGF(2 alpha) and TxA(2) release with no significant changes in PGE(2) and PGI(2) release. The NTG-induced CPP elevation was inhibited (P < 0.05) by indomethacin, a cyclooxygenase inhibitor? or ONO-3708, a TxA(2) receptor blocker, whereas arachidonic acid, a substrate for PG synthesis, augmented the CPP elevation. These results indicate that NTG stimulates the synthesis of vasoconstrictive PG in the O-2(-)-pretreated rat heart, inducing a paradoxical elevation in CPP.