Effects of N-acetylcysteine on nitroglycerin-induced relaxation and protein phosphorylation of porcine coronary arteries

We investigated the effects of the sulfhydryl-donor, N-acetylcysteine (NAC) , on nitroglycerin (NTG)-induced relaxation of the vascular smooth muscle. Addition of histamine to isolated porcine coronary arteries induced an init ial rapid contraction followed by a gradual decrease in tonic contraction. NTG applied to the coronary artery strips before histamine caused relaxatio n of the histamine-induced rapid (3 min) and tonic (48 min) contraction. Th e inhibition of the tonic contraction by NTG was less at 48 min than at 3 m in. Application of NAC (NTG-NAC) enhanced the relaxing effects of NTG on th e histamine-induced tonic contraction rather than the acute contraction. In phosphorylation studies, changes in the phosphorylation of an intermediate filament, desmin, were parallel with changes in contraction in NTG-treated and NTG-NAC samples at 48 min. These phosphorylation changes of desmin at 48 min, which might be responsible for tonic phase contraction, were more e xtensive than those of myosin light chain (MLC) phosphorylation at 3 min, w hich might be responsible for acute contraction. These results suggest that treatment with the sulfhydryl donor, NAG, inhibited the phosphorylation of desmin associated with the enhancement of NTG-induced relaxation, which mi ght be related to the mechanisms of recovery from NTG tolerance by sulfhydr yl groups.