S-nitrosothiol modulation of tolerance to glyceryl trinitrate in bovine isolated coronary artery

The aim of the study was to ascertain whether induction of tolerance to glyceryl trinitrate (GTN) was modified by nitrosothiols. Vasodilator responses to GTN and to two nitrosothiols, namely S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-N-acetylcaptopril (SNOCAP) were measured in bovine coronary artery rings constricted with the thromboxane mimetic agent U46619. Pre-exposure of vessels to SNAP (10 microM) for 1 h resulted in cross-tolerance to GTN comparable with tolerance induced by GTN (1.0 microM). Tolerance was increased after pre-exposure to both agents. SNAP alone in lower concentrations (0.01, 0.1 and 1.0 microM) did not produce cross tolerance to GTN, but in combination with GTN (1.0 microM) caused a small but significant decrease in tolerance to GTN. This attenuating effect of SNAP on GTN tolerance was reproduced by SNOCAP (0.01 microM). We conclude that the nitrosothiols exert a biphasic effect on induction of tolerance to GTN.