N-ACETYLCYSTEINE ENHANCES ENDOTHELIUM-DEPENDENT VASORELAXATION IN THEISOLATED RAT MESENTERIC-ARTERY

Study hypothesis: Previous studies have suggested that N-acetylcystein e (NAC) may confer additional protection in acetaminophen (APAP) overd ose by improving hepatic microcirculation. We hypothesize that NAC enh ances release of nitric oxide (NO) from the vasculature. Methods: Spra gue-Dawley rat superior mesenteric artery rings were suspended in oxyg enated Krebs-Henseleit tissue baths and contracted with U-46619 (a thr omboxane A(2)-mimetic). In part 1, the effect of NAC on endothelial ce ll (EC) release of NO was assessed by measurement of vasorelaxation in duced by acetylcholine (ACh, an EC-dependent vasorelaxor) in the prese nce and absence of NAG. In part 2, the effect of glutathione (a major component of NAC hepatoprotection) was examined by measuring ACh-induc ed vasorelaxation in rings from rat treated with L-buthionine sulfoxam ine (BSO, a glutathione synthesis inhibitor). Data were analyzed by re peated-measures ANOVA. Results: Addition of 15 to 30 mmol/l NAC after ring contraction had no direct vasodilatory effect. By contrast, pretr eatment of rings with NAC(15 mmol/L) enhanced vasorelaxation induced b y ACh (95.0%+/-7.9% versus 62.3%+/-7.6% for control; ACh dose, 1 mu mo l/L; P<.001) or by A23187, a receptor-independent, NO-mediated vasodil ator (91.6%+/-9.6% versus 68.3%+/-12.1% for control; A23187 dose, 1 mu mol/L; P<.001). In rings from BSO-treated rats, NAC also enhanced vas orelaxation (76.5%+/-7.1%; P<.001 versus control), but to a lesser deg ree than in nontreated rats. Conclusion: NAC enhances endothelium-depe ndent vasodilation in an isolated rat mesenteric artery ring preparati on. In addition to its antioxidant effects, NAC may decrease APAP hepa totoxicity by stimulating NO production and improving microvascular ci rculation.