Bl. Lopez et al., N-ACETYLCYSTEINE ENHANCES ENDOTHELIUM-DEPENDENT VASORELAXATION IN THEISOLATED RAT MESENTERIC-ARTERY, Annals of emergency medicine, 32(4), 1998, pp. 405-410
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.