缬沙坦对尼古丁损伤血管内皮依赖性舒张功能的保护作用及机制

摘要

Objective: To investigate the protective effect of valsartan on the endothelium-dependent relaxation (EDR)damage induced by nicotine in the isolated rat mesenteric arteries, and the mechanism thereof. Methods: The mesenteric artery rings of adult Sprague-Dawley rats were divided into 7 groups, control group (C group), nicotine group (N group, artery rings were cultured with 0.1 mmol /L nicotine ), valsartan group (V1, V2 and V3 group, artery rings were cultured with 0.1, 1 and 10μmol/L valsartan and 0.1 mmol/L nicotine), indomethacin and Nω-nitro-L-arginine (L-NAME) group (I group and L group, artery rings were cultured with 10 μmol/L valsartan, 0.1 mmol/L nicotine and 10 μmol/L indomethacin or 1 00 μmol/L L-NAME). The artery rings were cultured for 24 hours. The effects of different concentrations of acetylcholine (ACh)on the cultured-artery rings were measured. Results: There were significant differences in maximal endothelium-dependent relaxation (EDR) between N group and C group, N group and V2 group, N group and V3 group, V3 group and I group, V3 group and L group(P ＜ 0.05), except for ACh concentration( 10-9, 10-8.5 and 10-7 mol/L). Conclusion: Valsartan has protective effect on vascular EDR injury induced by nicotine, which may be related to the activation of nitric oxide and prostacyclin.%目的:探讨缬沙坦对尼古丁损伤大鼠肠系膜动脉内皮依赖性舒张反应的保护作用及机制.方法:将培养的成年SD大鼠肠系膜动脉环分为空白对照组(C组),尼古丁组(N组).缬沙坦低、中、高剂量组(V1、V2、V3组),吲哚美辛组(Ⅰ组)和L-Nω基精氨酸甲酯组(L组)7个组.尼古丁组将血管环与0.1 mmol/L尼古丁共同培养;缬沙坦组加入不同浓度(0.1、1、10μmol/L)缬沙坦与0.1 mmol/L尼古丁,共同培养;吲哚美辛组和L组加入10μmol/L缬沙坦、0.1mmol/L尼古丁与10 μmol/L吲哚美辛或10μmol/L L-Nω硝基精氨酸甲酯,共同培养.各组血管环均培养24 h.培养后,应用离体血管环张力描记法,研究不同浓度的乙酰胆碱(ACh)对血管内皮依赖性舒张反应的影响.结果:除ACh浓度(10-9、10-8.5、10-7mol/L)外,大鼠的血管最大舒张率N组与C、V2、V3组,V3组与Ⅰ组、L组之间差异均有统计学意义(P<0.05或P<0.01).结论:缬沙坦可能通过促进内皮细胞释放一氧化氮和前列环素而发挥保护尼古丁对血管内皮依赖性舒张功能损伤的作用.