N-Acetylcysteine Enhances Endothelium-Dependent Vasorelaxation in the Isolated Rat Mesenteric Artery

Study Hypothesis: Previous studies have suggested that N-Acetylcysteine (NAC) may confer additional protection in acetaminophen (APAP) overdose by improving hepatic microcirculation. We hypothesize that NAC enhances release of nitric oxide (NO) from the vasculature. Methods: Sprague-Dawley rat superior mesenteric artery rings were suspended in oxygenated Krebs-Henseleit tissue baths and contracted with U-46619 (a thromboxane A 2 -mimetic). In part 1, the effect of NAC on endothelial cell (EC) release of NO was assessed by measurement of vasorelaxation induced by acetylcholine (ACh, an EC-dependent vasorelaxor) in the presence and absence of NAC. In part 2, the effect of glutathione (a major component of NAC hepatoprotection) was examined by measuring ACh-induced vasorelaxation in rings from rats treated with l-buthionine sulfoxamine (BSO, a glutathione synthesis inhibitor). Data were analyzed by repeated-measures ANOVA. Results: Addition of 15 to 30 mmol/L NAC after ring contraction had no direct vasodilatory effect. By contrast, pretreatment of rings with NAC (15 mmol/L) enhanced vasorelaxation induced by ACh (95.0%±7.9% versus 62.3%±7.6% for control; ACh dose, 1 μmol/L; P