Browse > Article

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

Kim, Soo-Wan (Chonnam National University Research Institute of Medical Sciences)
Lee, Jong-Un (Chonnam National University Research Institute of Medical Sciences)
Han, Sang-Woong (Department of Internal Medical, Hanyang University)
Ryu, Jun-Ho (Department of Internal Medical, Hanyang University)
Oh, Yoon-Wha (Chonnam National University Research Institute of Medical Sciences)
Kim, Nam-Ho (Chonnam National University Research Institute of Medical Sciences)
Choi, Ki-Chul (Chonnam National University Research Institute of Medical Sciences)
Kim, Ho-Jung (Department of Internal Medical, Hanyang University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.6, no.2, 2002 , pp. 127-130 More about this Journal
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 $(TGF)-{\beta}1$ 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 $(TGF)-{\beta}1$ 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.
Keywords
Adriamycin; Renin; Angiotensin converting enzyme; Type 1 and type 2 angiotensin II receptors; Transforming growth $factor-{\beta}1$;
Citations & Related Records

Times Cited By SCOPUS : 0
연도 인용수 순위
  • Reference
1 Fukuda K, Yoshitomi K, Yanagida T, Tokumoto M, Hirakata H. Quantification of TGF-$\beta$1 mRNA along rat nephron in obstructive nephropathy. Am J Physiol 281: F513－F521, 2001
2 Hirsch AT, Talsness CE, Smith AD, Schunkert H, Ingelfinger JR, Dzau VJ. Differential effects of captopril and enalapril on tissue rennin-angiotensin systems in experimental heart failure. Circulation 86: 1566－1574, 1992   DOI   PUBMED   ScienceOn
3 Nakamura T, Obata J, Kimura H, Ohno S, Yoshida Y, Kawachi H, Shimizu F. Blocking angiotensin II ameliorates proteinuria and glomerular lesions in progressive mesangioproliferative glomerulonephritis. Kidney Int 55: 877－889, 1999   DOI   ScienceOn
4 Neimir Z, Stein H, Noronha I, Kruger C, Andrassy K, Ritz E, Waldherr R. PDGF and TGF-$\beta$ contribute to the natural course of human IgA glomerulonephritis. Kidney Int 48: 1530－1541, 1995   DOI   ScienceOn
5 Passier RC, Smits JF, Verluyten MJ, Studer R, Drexler H, Daemen MJ. Activation of angiotensin converting enzyme expression in infarct zone following myocardial infarction. Am J Physiol 269: H1268－H1276, 1995   PUBMED
6 Tsutsumi Y, Matsubara H, Masaki H, Kurihara H, Murasawa S, Takai S, Miyazaki M, Nozawa Y, Ozono R, Nakagawa K, Miwa T, Kawada N, Mori Y, Shibasaki Y, Tanaka Y, Fujiyama S, Koyama Y, Fujiyama A, Takahashi H, Iwasaka T. Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. J Clin Invest 104: 925－935, 1999   DOI   ScienceOn
7 Gomez RA, Lynch KR, Chevalier RL, Everett AD, Johns DW, Wilfong N, Peach MJ, Carey RM. Renin and angiotensinogen gene expression and intrarenal renin distribution during ACE inhibition. Am J Physiol 254: F900－F906, 1988   PUBMED
8 Lafayette RA, Mayer G, Park SK, Meyer TW. Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass. J Clin Invest 90: 766－771, 1992   DOI   PUBMED
9 Anderson S. Physiologic actions and molecular expression of the renin-angiotensin system in the diabetic rat. Miner Electrolyte Metab 24: 406－411, 1998   DOI   PUBMED   ScienceOn
10 Tank JE, Moe OW, Henrich WL. Abnormal regulation of proximal tubule renin mRNA in the Dahl/Rapp salt-sensitive rat. Kidney Int 54: 1608－16, 1998   DOI   ScienceOn
11 Mistry SK, Chatterjee PK, Weerackody RP, Hawksworth GM, Knott RM, McLay JS. Evidence for atrial natriuretic factor induced natriuretic peptide receptor subtype switching in rat proximal tubular cells during cell culture. Exp Nephrol 6: 101－ 111, 1998
12 Wolf G, Mueller E, Stahl RAK, Ziyadeh FN. Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-b. J Clin Invest 92: 1366－1372, 1993   DOI   ScienceOn
13 Endo Y, Arima S, Yaoita H, Tsunoda K, Omata K, Ito S. Vasodilation mediated by angiotensin II type 2 receptor is impaired in afferent arterioles of young spontaneously hypertensive rats. J Vasc Res 35: 421－427, 1998   DOI   ScienceOn
14 Arima S, Endo Y, Yaoita H, Omata K, Ogawa S, Tsunoda K, Abe M, Takeuchi K, Abe K, Ito S. Arima S, Endo Y, Yaoita H, Omata K, Ogawa S, Tsunoda K, Abe M, Takeuchi K, Abe K, Ito S. Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole. J Clin Invest 100: 2816－2823, 1997   DOI   ScienceOn
15 Kastner PR, Hall JE, Guyton AC. Control of glomerular filtration rate: Role of intrarenally formed angiotensin II. Am J Physiol 246: F897－F906, 1984
16 Hunley TE, Tamura M, Stoneking BJ, Nishimura H, Ichiki T, Inagami T, Kon V. The angiotensin type II receptor tonically inhibits angiotensin-converting enzyme in AT2 null mutant mice. Kidney Int 57: 570－577, 2000   DOI   ScienceOn
17 Li J, Zhou C, Yu L, Wang H. Renal protective effects of blocking the intrarenal renin-angiotensin system. Hypertens Res 22: 223 －228, 1999   DOI   ScienceOn
18 Kagami S, Border WA, Miller DE, Noble NA. Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-b expression in rat glomerular mesangial cells. J Clin Invest 93: 2431－2437, 1994   DOI   ScienceOn
19 Kitami Y, Okura T, Marumoto K, Wakamiya R, Hiwada K. Differential gene expression and regulation of type-1 angiotensin II receptor subtypes in the rat. Biochem Biophys Res Commun 188: 446－452, 1992   DOI   ScienceOn
20 Anderson S, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Invest 77: 1993－2000, 1986   DOI   PUBMED
21 Wu LL, Cox A, Roe CJ, Dziadek M, Cooper ME, Gilbert RE. Transforming groth factor b1 and renal injury following subtotal nephrectomy in the rat: Role of the renin-angiotensin system. Kidney Int 51: 1553－1567, 1997   DOI   ScienceOn
22 Hall RL, Wilke WL, Fettman MJ. The progression of adriamycininduced nephritic syndrome in rats and the effect of captopril. Toxicol Appl Pharmacol 82: 164－174, 1986   DOI   ScienceOn
23 Negoro N, Kanayama Y, Iwai J, Umetani N, Nishimura M, Konishi Y, Okamura M, Inoue T, Takeda T. Angiotensin-converting enzyme inhibitor increases angiotensin type 1A receptor gene expression in aortic smooth muscle cells of spontaneously hypertensive rats. Biochim Biophys Acta 1226: 19－24, 1994
24 Yamamoto T, Nakamura T, Noble NA, Ruoslahti E, Border WA. Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy. Proc Natl Acad Sci USA 90: 1814－1818, 1993   DOI   ScienceOn
25 Okuda S, Oh Y, Tsuruda H, Onoyama K, Fujimi S, Fujishima M. Adriamycin-induced nephropathy as a model of chronic progressive glomerular disease. Kidney Int 29: 502－510, 1986   DOI   ScienceOn
26 Nakamura N, Soubrier F, Menard J, Panthier JJ, Rougeon F, Corvol P. Nonproportional changes in plasma renin concentration, renal renin content, and rat renin messenger RNA. Hypertension 7: 855－859, 1989
27 Noble NA, Border WA. Angiotensin II in renal fibrosis: should TGF- $\beta$ rather than blood pressure be the therapeutic target. Semin Nephrol 17: 455－466, 1997   PUBMED
28 Ruiz-Ortega M, Egido J. Angiotensin II modulates cell growthrelated events, and synthesis of matrix proteins in renal interstitial fibrosis. Kidney Int 52: 1497－1510, 1997   DOI   ScienceOn
29 Kakinuma Y, Kawamura T, Bills T, Yoshioka T, Ichikawa I, Fogo A. Blood pressure-independent effect of angiotensin inhibition on vascular lesions of chronic renal failure. Kidney Int 42: 46－ 55, 1992   DOI   ScienceOn
30 Miyata N, Park F, Li XF, Cowley AW Jr. Distribution of angiotensin AT1 and AT2 receptor subtypes in the rat kidney. Am J Physiol 277: F437－F446, 1999   PUBMED
31 Gasc JM, Monnot C, Clauser E, Corvol P. Co-expression of type I angiotensin II receptor (AT1R) and rennin mRNAs in juxtaglomerular cells of rat kidney. Endocrinology 132: 2723－ 2725, 1993   DOI   ScienceOn