Tate Y, Kawasaki K, Ishibashi S, Ikeda U, Shimada K
Department of Cardiology, Jichi Medical School, Minamikawachi-machi, Tochigi, Japan.
Heart Vessels. 1998;13(6):263-8. doi: 10.1007/BF03257230.
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 initial rapid contraction followed by a gradual decrease in tonic contraction. NTG applied to the coronary artery strips before histamine caused relaxation of the histamine-induced rapid (3 min) and tonic (48 min) contraction. The inhibition of the tonic contraction by NTG was less at 48 min than at 3 min. Application of NAC (NTG-NAC) enhanced the relaxing effects of NTG on the 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 extensive than those of myosin light chain (MLC) phosphorylation at 3 min, which might be responsible for acute contraction. These results suggest that treatment with the sulfhydryl donor, NAC, inhibited the phosphorylation of desmin associated with the enhancement of NTG-induced relaxation, which might be related to the mechanisms of recovery from NTG tolerance by sulfhydryl groups.
我们研究了巯基供体N-乙酰半胱氨酸（NAC）对硝酸甘油（NTG）诱导的血管平滑肌舒张的影响。向离体猪冠状动脉中加入组胺会引起最初的快速收缩，随后张力性收缩逐渐减弱。在组胺作用前将NTG应用于冠状动脉条，可使组胺诱导的快速（3分钟）和张力性（48分钟）收缩舒张。NTG对48分钟时张力性收缩的抑制作用小于3分钟时。应用NAC（NTG-NAC）增强了NTG对组胺诱导的张力性收缩而非急性收缩的舒张作用。在磷酸化研究中，中间丝结蛋白的磷酸化变化与48分钟时NTG处理和NTG-NAC样本中的收缩变化平行。48分钟时结蛋白的这些磷酸化变化可能与张力性收缩有关，比3分钟时肌球蛋白轻链（MLC）磷酸化变化更广泛，后者可能与急性收缩有关。这些结果表明，巯基供体NAC处理抑制了结蛋白的磷酸化，同时增强了NTG诱导的舒张作用，这可能与巯基从NTG耐受性中恢复的机制有关。
