アンジオテンシンⅡ受容体拮抗薬(TCV-116)の心肥大抑制効果 : 自然発症高血圧ラット(SHR)での検討

Abstract

The renin-angiotensin system is an important hormonal system that regu- lates volume and fluid homeostasis. Recently, it has been suggested that angiotensinⅡ (A Ⅱ)may directly cause cardiac hypertrophy and fibrosis by acting on myocardial cells. I investigated the preventive effect of an AⅡ reseptor antagonist(TCV-116)on the develop- ment of cardiac hypertrophy and fibrosis in spontaneously hypertensive rats(SHR) at 16 and 24 weeks of age through histopathological study, an AⅡ receptor assay and studies of type -1 angiotensin Ⅱ (AT-1)receptor messenger RNA(mRNA)expression. AⅡ receptor den- sity was determined by radiobinding immunoassay. The expression of AⅡ receptor mRNA in myocardial cells was determined by reverse transcriptase-polymerase chain reaction(rt -PCR). The groups of treatment with TCV-116, ACE inhibitor(enalapril)and hydralazine at 8, 16 and 24 weeks of age showed significantly lower systolic blood pressure than the no treatment group. The heart weight/ body weight ratio, the diameter of myocardium and the percent area of myocardial fibrosis were significantly lower in the group of treatment with enalapril and TCV-116 than the group of treatment with hydralazine and non medicated SHR at 16 and 24 weeks of age. The density of AⅡ receptor and the expression of AT-1 receptor mRNA were significantly higher in the group of treatment with enalapril and TCV-116 than the group of treatment with hydralazine and non medicated SHR at 24 weeks of age. The present study suggests that angiotensin Ⅱ may be involved in the development of cardiac hypertrophy and fibrosis in SHR, and that the AⅡ receptor antagonist inhibited the progression of cardiac hypertrophy and fibrosis via the AⅡ receptor, and that the density of AⅡ receptor and the expression of AT-1 receptor mRNA may be regulated by the stimulus to AⅡ receptor.