内皮源舒张因子合成抑制剂致大鼠心血管变化及意义  

Significance and Cardiovascular Changes Induced by Inhibition of Endothelium Derived Relaxing Factor Synthesis in Rats

作　　者：高连如[1] 刘国仗[1] 赵云涛[1] 石湘芸[1] 熊然 杨晔[1] 张继峰[1] 田青[1] 宫长宁 唐朝枢[1] 汤健[1] 

机构地区：[1]中国人民解放军海军总医院心内科,北京医科大学心肺内分泌研究室

出　　处：《中国循环杂志》1996年第5期300-303,共4页Chinese Circulation Journal

摘　　要：目的：探讨内皮源舒张因子（ＥＤＲＦ）合成受抑制时的心血管病理生理的变化及意义。方法：实验组大鼠（ｎ＝６）长期应用ＥＤＲＦ抑制剂──Ｌ－硝基精氨酸１５ｍｇ，ｋｇ^（－１）／ｄ，腹腔注射，共２８天），对照组（ｎ＝６）给予注射用水。结果：与对照组比较，Ｌ－硝基精氨酸使大鼠血压明显增高、心率减慢、心功能增强，主动脉环对去甲肾上腺素（１０^（１１）～１０^（－５）ｍｏｌ／Ｌ）和内皮素（１０^（－１０）～１０^（－６）ｍｏｌ／Ｌ）的收缩反应增强（Ｐ＜０．０５），对乙酰胆碱（１０^（－９）～１０^（－５）ｍｏｌ／Ｌ）和降钙素基因相关肽（１０^（－１０）～１０^（－８）ｍｏｌ／Ｌ）舒张反应减弱（Ｐ均＜０．０５），血浆和组织内皮素增高，主动脉组织环磷酸鸟苷活性减低，血浆血管紧张素Ⅱ和肾素活性减低，血浆丙二醛增高。肾入球小动脉内膜增厚。结论：ＥＤＲＦ对心血管有重要调控功能，ＥＤＲＦ减少可导致心血管一系列病理生理变化。Objective:To investigate the changes and significance of cardiovascular pathophysioglogy induced by inhibition of endothelium derived relaxing factor(EDRF) synthesis in rats.Methods:NG-Nitro-L-Arginine(L-NNA,15mg· kg(-1)/day ) and distilled water were administrated by intraperitoneal injection to Wistar rats of the experimental (n=6)and control (n=6)groups,respectively for 28 days.Results:Comparing with the control group,the L-NNA group was found to have severely sustained hypertension(p< 0.01) with bradycardia(p< 0. 05);Cardiac function was increased by compensation;heart weight was markedly increased; Maximal contractions of aortic rings to ET(10(-10)-10(-6) mol/L)and NE(10(-11)-10(-5)mol/L)were significantly augmented and dose dependent relaxations by Ach (10(-9)-10(-5) mol/L)and CGRP(10(-10)-2×10(-8)mol/L)was markedly decreased(all p<0. 05);The levels of plasma and aortic ET were much higher and aortic cGMP activity was much lower(all p<0. 01);Plasma Ang Ⅱ and PRA were reduced (p<0.05); Plasma MDA was increased (p<0.05)and renal preglomerular arterioles showed intimal thickening.Conclusion:These data strongly support the hypothesis that endothelial production of EDRF is an important basal regulator of blood pressure homeostasis.The reduction of EDRF can induce hypertension and a series of changes in cardiovascular pathophysiology.

关 键 词：内皮源舒张因子 病理生理 心血管疾病 

分 类 号：R540.2[医药卫生—心血管疾病]