Korean J Physiol Pharmacol.  2002 Apr;6(2):127-130.

Upregulation of Renal Renin-Angiotensin System in Rats with Adriamycin-Induced Nephrosis

• Kim SW
• Lee JU
• Han SW
• Ryu JH
• Oh YW
• Kim NH
• Choi KC
• Kim HJ

Abstract

The present study was aimed to investigate whether the adriamycin-induced nephrosis is associated with an altered regulation of local renin-angiotensin system (RAS) in the kidney. Rats were subjected to a single injection of adriamycin (2 mg/kg body weight, IV) and kept for 6 weeks to allow the development of nephrosis. They were then divided into two groups, and supplied with and without cilazapril, an angiotensin converting enzyme (ACE) inhibitor, in drinking water (100 mg/l) for additional 6 weeks. Another group without adriamycin-treatment served as control. The mRNA expression of renin, ACE, type 1 and type 2 angiotensin II receptors (AT1R, AT2R), and transforming growth factor (TGF) -beta1 was determined in the cortex of the kidney by reverse transcription-polymerase chain reaction. Adriamycin treatment resulted in heavy proteinuria. Accordingly, the mRNA expression of renin, ACE, and AT1R was increased in the renal cortex, while that of AT2R was decreased. Co-treatment with cilazapril attenuated the degree of proteinuria. While not affecting the altered expression of renin, cilazapril decreased the expression of ACE to the control level. Cilazapril further increased the expression of AT1R, while it restored the decreased expression of AT2R. The expression of TGF-beta1 was increased by the treatment with adriamycin, which was abolished by cilazapril. An altered expression of local RAS components may be causally related with the development of adriamycin-induced nephrosis, in which AT1R is for and AT2R is against the development of nephrosis.

Keyword

Adriamycin; Renin; Angiotensin converting enzyme; Type 1 and type 2 angiotensin II receptors; Transforming growth factor-beta1

MeSH Terms

Animals
Body Weight
Cilazapril
Doxorubicin
Drinking Water
Kidney
Nephrosis*
Peptidyl-Dipeptidase A
Proteinuria
Rats*
Receptors, Angiotensin
Renin
Renin-Angiotensin System*
RNA, Messenger
Transforming Growth Factor beta1
Transforming Growth Factors
Up-Regulation*
Cilazapril
Doxorubicin
Drinking Water
Peptidyl-Dipeptidase A
RNA, Messenger
Receptors, Angiotensin
Renin
Transforming Growth Factor beta1
Transforming Growth Factors