Wu M, Pritchard K A, Kaminski P M, Fayngersh R P, Hintze T H, Wolin M S
Department of Experimental Pathology, New York Medical College, Valhalla 10595.
Am J Physiol. 1994 May;266(5 Pt 2):H2108-13. doi: 10.1152/ajpheart.1994.266.5.H2108.
Peroxynitrite (ONOO-) is an inflammatory cell-derived oxidant, formed by the reaction of superoxide anion (O2-) with nitric oxide (NO), which was recently reported to relax vascular tissues. In the present study, the potential role of NO in the mechanism of relaxation in isolated bovine endothelium-denuded pulmonary arterial smooth muscle rings to ONOO- was evaluated. Potassium-preconstricted pulmonary arterial rings rapidly relaxed for a prolonged period of time on exposure to ONOO- (0.01-0.1 mM). The relaxation after 1 min of exposure to ONOO- (0.1 mM) was reduced 49 and 87%, respectively, by inhibitors of the stimulation of soluble guanylate cyclase, methylene blue, and LY-83583. In contrast, a scavenger of hydroxyl radicals, dimethyl sulfoxide, did not alter this response. Decomposed 0.1 mM ONOO- (which is primarily nitrite) and 0.1 mM nitrite caused a relaxation of pulmonary artery, which slowly developed over 15 min. Small quantities of NO were detected by chemiluminescence quantification methods when ONOO- was added to buffer. Exposure of pulmonary arterial tissue or buffer containing glutathione (GSH) to ONOO- caused a time-dependent increase in the observed generation of NO, whereas decomposed ONOO- produced 10% of the NO generated by ONOO- on incubation with pulmonary arterial tissue. Treatment with diethyl maleate, an agent that depletes tissue GSH, reduced both the relaxation and the formation of NO detected from pulmonary artery on exposure to ONOO-. GSH solutions treated with ONOO- appear to have generated a nitrosothiol-like vascular relaxant compound. Thus ONOO- appears to relax vascular tissue, in part, by nitrosylating tissue GSH (or other thiols), which subsequently releases NO over prolonged time periods.
过氧亚硝酸根（ONOO⁻）是一种由炎症细胞产生的氧化剂，由超氧阴离子（O₂⁻）与一氧化氮（NO）反应形成，最近有报道称其可使血管组织舒张。在本研究中，评估了NO在离体牛去内皮肺动脉平滑肌环对ONOO⁻舒张机制中的潜在作用。用钾预收缩的肺动脉环在暴露于ONOO⁻（0.01 - 0.1 mM）后迅速且长时间舒张。暴露于ONOO⁻（0.1 mM）1分钟后的舒张分别被可溶性鸟苷酸环化酶刺激抑制剂亚甲蓝和LY - 83583降低了49%和87%。相比之下，羟自由基清除剂二甲基亚砜并未改变这种反应。分解的0.1 mM ONOO⁻（主要是亚硝酸盐）和0.1 mM亚硝酸盐导致肺动脉舒张，这种舒张在15分钟内缓慢发展。当向缓冲液中添加ONOO⁻时，通过化学发光定量方法检测到少量的NO。肺动脉组织或含有谷胱甘肽（GSH）的缓冲液暴露于ONOO⁻会导致观察到的NO生成随时间增加，而分解的ONOO⁻在与肺动脉组织孵育时产生的NO仅为ONOO⁻产生量的10%。用马来酸二乙酯（一种消耗组织GSH的试剂）处理可降低暴露于ONOO⁻时肺动脉的舒张和检测到的NO形成。用ONOO⁻处理的GSH溶液似乎产生了一种类似亚硝基硫醇的血管舒张化合物。因此，ONOO⁻似乎部分通过使组织GSH（或其他硫醇）亚硝基化来舒张血管组织，随后在较长时间内释放NO。
