摘要
目的：探讨醛固酮受体拮抗剂螺内酯（ｓｐｉｒｏｎｏｌａｃｔｏｎｅ，安体舒通）预防一氧化氮减少致高血压心肌重塑的可行性。方法：取８周龄雄性Ｗｉｓｔａｒ大鼠１９只，随机分成高血压大鼠实验组１２只，其中又分为高血压组、预防组各６只；正常血压对照组７只。高血压大鼠实验组用Ｌ－硝基精氨酸（Ｎ－ｏｍｅｇａ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ，ＬＮＮＡ，７．５ｍｇ／ｋｇ，腹腔注射，每日２次，共４周）诱导高血压心肌重塑大鼠１２只，其中６只同时以安体舒通（２０ｍｇ／ｋｇ，每日１次，灌胃，共４周）治疗。分别观察其动脉血压、左心室相对重量、丝裂素活化蛋白激酶（ｍｉｔｏｇｅｎ－ａｃｔｉｖａｔｅｄｐｒｏｔｅｉｎｋｉｎａｓｅ，ＭＡＰＫ）活性、胶原蛋白含量、亚硝酸盐浓度、心肌组织形态学改变等。结果：高血压组亚硝酸盐浓度降低，血压、ＭＡＰＫ活性及胶原蛋白含量均明显升高，左心室肥大，心肌细胞肥大及心肌纤维化。安体舒通可明显降低动脉压、ＭＡＰＫ活性，减轻左心室肥大、心肌细胞肥大及心肌纤维化。结论：安体舒通通过竞争性抑制醛固酮与其受体结合，降低ＭＡＰＫ活性，可防止一氧化氮生成减少所致高血压心肌重塑及血压持续升高。
? Objective:To detect the effect of aldosterone(Aldo) receptor antagonist,spironolactone(spiron),on the prevention of hypertensive myocardial remodeling induced by the decrease of nitric oxide(NO). Methods:We examed the arterial pressure,the left ventriclebody weight ratio(LVR),tissue content of collagen,activity of tissue mitogenactivated protein kinase(MAPK),the serum level of the metabolite of NO,nitrate(NO-2),myocardial morphologic changes and so on in 12 16weekold sustained hypertensive Wistar rats induced by Larginine analogue NomeganitroLarginine (LNNA,75 mg/kg,i.p.bid for 4 weeks)(including 6 hypertensive rats treated with 20 mg/kg spiron by gavage once a day at same time) and in 7 normotensive agesexmatched Wistar rats,respectively. Results:There were significant increases in systolic,diastolic and mean arterial blood pressures,LVR,tissue content of collagen and tissue activity of MAPK;a significant decrease in serum NO-2;myocyte hypertrophy and cardiac fibrosis in the hypertensive group as compared with the control group.The spiron treatment significantly attenuated the arterial pressures,LVR,collagen content,MAPK activity and the pathologic changes in the hypertensive rats. Conclusion:These data show that the spiron is a competitive antagonist which inhibits Aldo binding with its specific receptor sites in cardiac tissue therefore diminishes the biologic activity of MAPK,then induces the regression of myocardial remodeling and hypertension in LNNAinduced hypertensive rats.
出处
《中国循环杂志》
CSCD
北大核心
1997年第6期456-458,共3页
Chinese Circulation Journal
关键词
高血压
心肌重塑
螺内酯
硝基精氨酸
预防
Hypertensive myocardial remodeling
Spironolactone
NomeganitroLarginine
