Effects of Angiotensin Converting Enzyme Inhibition on Gene Expression of the Renin-Angiotensin System in Rats

• 영문명: Effects of Angiotensin Converting Enzyme Inhibition on Gene Expression of the Renin-Angiotensin System in Rats
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Young Rae Lee Mi Young Lee Woon Jung Kim Won Jung Lee
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제2권 제6호, 771~778쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 1998.01.01

영문 초록

To investigate interaction of angiotensin converting enzyme (ACE) inhibitor with local tissue renin- angiotensin system (RAS), changes in gene expression of the RAS components in various tissues in response to chronic administration of an ACE inhibitor, enalapril, were examined in Sprague-Dawley male rats. Enalapril was administered in their drinking water (3∼4 mg/day) over 8 wk. Plasma and renal ACE activity increased significantly after 4 and 8 wk of enalapril treatment. Renin levels of the plasma and kidney of the enalapril-treated rats markedly increased after 4 wk and decreased thereafter, but still remained significantly higher than those of control rats. Kidney mRNA levels of renin markedly increased after 4 and 8 wk of enalapril treatment, but those of angiotensinogen and ANG II-receptor subtypes, AT_1A and AT_1B, did not change significantly. The liver expressed genes for renin, angiotensinogen and AT_1A receptor subtype, but AT_1B receptor subtype mRNA was not detectable by RT-PCR. None of mRNA for these RAS components in the liver changed significantly by enalapril treatment. The hypothalamus showed mRNA expressions of renin, angiotensinogen, AT_1A and AT_1B receptor subtypes. AT_1A receptor subtype mRNA was more abundant than AT_1B receptor subtype in the hypothalamus as shown in the kidney. However, gene expression of the RAS components remained unchanged during 8-wk treatment of enalapril. In the present study, chronic ACE inhibition increased plasma and renal levels of ACE and renin, but did not affect mRNA levels of other RAS components such as angiotensinogen, ANG II receptor subtypes in the kidney. Gene levels of the RAS components in the liver and hypothalamus were not altered by chronic treatment of enalapril. These results suggest the differential expression of the RAS components in response to enalapril, and localized action and some degree of tissue specificity of enalapril.

키워드

Enalapril Northern blot RT-PCR Kidney Liver Brain