摘要
目的研究长期应用(4wk)卡托普利(30mg·kg-1)、依那普利(20mg·kg-1)和福辛普利(20mg·kg-1)3种血管紧张素转换酶抑制剂(ACEI)对自发性高血压大鼠(SHR)肾功能的影响以及与肾素-血管紧张素-醛固酮系统(RAA)、激肽释放酶-激肽系统(K-K)及前列腺素系统(PGS)的可能关系。方法测定血清及尿中的肌酐以计算肾小球滤过率、用放免法测定上述系统中有关活性物质在血浆、肾脏及尿中的浓度。结果3种ACEI均显著地降低SHR的血压。依那普利及福辛普利处理后SHR肌酐清除率分别为(370±112)及(380±110)ml·d-1,高于未处理SHR的滤过率(260±110,P<0.05)。SHR用依那普利或福辛普利处理后血浆肾素活性及血管紧张素系Ⅰ(ATⅠ)浓度分别为(41±38)、(17±7)nmol·L-1·h-1及(12±8)、(14±10)nmol·L-1。肾脏肾素活性及ATⅠ浓度分别为(146±27)、(139±31)nmol·g-1蛋白·h-1及(85±25)、(95±23)nmol·g-1蛋白,均高于未处理组(P<0.05)。SHR尿醛固酮排泄量在用卡托普利或依那普利处理后分别为(0.9±0.7)及(0.9±0.6)nmol·d-1,降至正常大鼠的水平,且低于未处理SHR(P<0.05)。结论RAA在ACEI改善肾脏功能作用中起主要作用,而K-K及PGs不起重要作用。
AIM To study the effects on renal function of chronic administratio (4 week) of captopril (30 mg·kg-1),enalapril (20 mg·kg-1) and fosinopril (20 mg·kg-1) in spontaneously hypertensive rats (SHR). The possible relationships of these effects with renin-angiotensin-aldosterone system (RAA), kallikrein-kinin system (KK) and prostaglandin system (PGs ) also were studied. METHODS The clearance of creatinine was regarded as the glomerular filtration rate. The active substances in RAA, KK and PGs were determined with radioimmunoannalysis. RESULTS After treatment with enalapril and fosinopril, the clearance of creatinine in SHR was (370 ± 112 ) and (380 ± 110) ml·d-1. These values were significantly higher than the values in untreated SHR (260 ± 110, P<0. 05 ). The renin activity and angiotensin Ⅰ contents in plasma or kidney of SHR treated with enalapril and fosinopril were higher than ones of untreated SHR. They were (41 ± 28) nmol· L-1· h-1 (PRA), (12 ± 8) nmol· L-1 (PATI), (146± 27) nmol· g-1 protein. h (RRA), 85 ± 25 nmol· g-1 protein (in SHR treated with enalapril ) and 17 ± 7, 14±10, 139 ± 31, 95 ± 23 (in SHR treated with fosinopril) and 10±5, 3± 1. 9, 50 ± 36, 52 ± 15 (in untreated SHR ), respectively. The differences between treated and untreated SHR were statistically significant (P<0. 05). The urinary aldosterone in SHR with treatment of enalapril or fosinopril was (0. 9 ± 0. 7) and (0. 9 ± 0. 6) μ mol· d-1 and lower than the that in untreated SHR (1. 4 ± 0. 6, P<0. 05). Any significant changes on urinary kallikrein and bradykinin, and PGE, 6-keto-PGF1α and their ratio in plasma, urinary or kidney of SHR after chronic administration of ACEI were not found. CONCLUSION RAA has principal place in the improvement on renal fuction of ACEI, but KK or PGs do not play an important role in it.
出处
《中国药理学通报》
CAS
CSCD
北大核心
1998年第5期458-461,共4页
Chinese Pharmacological Bulletin
基金
国家自然科学基金!39170848
关键词
高血压
肾功能
药物疗法
ACEI
angiotensin converting enzyme inhibitor
renal function
renin-angiotensin-aldosterone system