Protective effect of N-acetylcysteine against oxygen radical-mediated coronary artery injury

the present study investigated the protective effect of n-acetylcysteine (nac) against oxygen radical-mediated coronary artery injury. vascular contraction and relaxation were determined in canine coronary arteries immersed in kreb's solution (95% o2-5% co2), incubated or not with nac (10 mm), and exposed to free radicals (fr) generated by xanthine oxidase (100 mu/ml) plus xanthine (0.1 mm). rings not exposed to fr or nac were used as controls. the arteries were contracted with 2.5 μm prostaglandin f2a. subsequently, concentration-response curves for acetylcholine, calcium ionophore and sodium fluoride were obtained in the presence of 20 μm indomethacin. concentration-response curves for bradykinin, calcium ionophore, sodium nitroprusside, and pinacidil were obtained in the presence of indomethacin plus nw-nitro-l-arginine (0.2 mm). the oxidative stress reduced the vascular contraction of arteries not exposed to nac (3.93 ± 3.42 g), compared to control (8.56 ± 3.16 g) and to nac group (9.07 ± 4.0 g). additionally, in arteries not exposed to nac the endothelium-dependent nitric oxide (no)-dependent relaxation promoted by acetylcholine (1 nm to 10 μm) was also reduced (maximal relaxation of 52.1 ± 43.2%), compared to control (100%) and nac group (97.0 ± 4.3%), as well as the no/cyclooxygenase-independent receptor-dependent relaxation provoked by bradykinin (1 nm to 10 μm; maximal relaxation of 20.0 ± 21.2%), compared to control (100%) and nac group (70.8 ± 20.0%). the endothelium-independent relaxation elicited by sodium nitroprusside (1 nm to 1 μm) and pinacidil (1 nm to 10 μm) was not affected. in conclusion, the vascular dysfunction caused by the oxidative stress, expressed as reduction of the endothelium-dependent relaxation and of the vascular smooth muscle contraction, was prevented by nac.