Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney

Alda Tufro-Mcreddie, R. Ariel Gomez, Laura L. Norling, Alaaedin A. Omar, Leon C. Moore, Frederick J. Kaskel

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

To determine whether Cyclosporine A (CsA) alters the intrarenal expression of the renin and type 1 angiotensin II receptor genes, male adult Sprague-Dawley rats were given 25 mg/kg/ day CsA s.c. for three weeks (CsA, N = 20) and were compared to pair-fed vehicle treated rats (Con, N = 20). The intrarenal distribution of renin and its mRNA was assessed by immunocytochemistry and in situ hybridization. In addition, kidney renin and type 1 angiotensin II (AT1) receptor mRNA levels were determined by Northern blot analysis. The percentage of juxtaglomerular apparatuses containing renin was higher in the CsA (84 ± 5.5%) than in the Con (61 ± 6.7%) group, (P < 0.05). The length of renin immunostaining along afferent arterioles was higher in the CsA (74 ± 4.5 μm) than in the Con (37 ± 5.1 μm) group, (P < 0.05). In contrast, neither renin mRNA levels nor its intrarenal distribution were altered by chronic CsA administration. Kidney AT1 receptor mRNA levels were lower in the CsA group than in the Con group. We conclude that chronic CsA: (1) induces recruitment of renin containing cells along the afferent arteriole, (2) causes no changes in intrarenal renin mRNA levels or distribution, suggesting that post-transcriptional events may be responsible for the persistence and/or uptake of renin by the preglomerular vasculature, (3) promotes a downregulation of AT1 receptor gene in the kidney, suggesting that local angiotensin II may control AT1 receptor gene expression by a negative feedback.

Original languageEnglish (US)
Pages (from-to)615-622
Number of pages8
JournalKidney International
Volume43
Issue number3
StatePublished - Mar 1993
Externally publishedYes

Fingerprint

Angiotensin Type 1 Receptor
Renin
Cyclosporine
Kidney
Genes
Messenger RNA
Arterioles
Juxtaglomerular Apparatus
Angiotensin Receptors
Angiotensin II
Northern Blotting
In Situ Hybridization
Sprague Dawley Rats
Down-Regulation
Immunohistochemistry
Gene Expression

ASJC Scopus subject areas

  • Nephrology

Cite this

Tufro-Mcreddie, A., Gomez, R. A., Norling, L. L., Omar, A. A., Moore, L. C., & Kaskel, F. J. (1993). Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney. Kidney International, 43(3), 615-622.

Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney. / Tufro-Mcreddie, Alda; Gomez, R. Ariel; Norling, Laura L.; Omar, Alaaedin A.; Moore, Leon C.; Kaskel, Frederick J.

In: Kidney International, Vol. 43, No. 3, 03.1993, p. 615-622.

Research output: Contribution to journalArticle

Tufro-Mcreddie, A, Gomez, RA, Norling, LL, Omar, AA, Moore, LC & Kaskel, FJ 1993, 'Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney', Kidney International, vol. 43, no. 3, pp. 615-622.
Tufro-Mcreddie A, Gomez RA, Norling LL, Omar AA, Moore LC, Kaskel FJ. Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney. Kidney International. 1993 Mar;43(3):615-622.
Tufro-Mcreddie, Alda ; Gomez, R. Ariel ; Norling, Laura L. ; Omar, Alaaedin A. ; Moore, Leon C. ; Kaskel, Frederick J. / Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney. In: Kidney International. 1993 ; Vol. 43, No. 3. pp. 615-622.
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abstract = "To determine whether Cyclosporine A (CsA) alters the intrarenal expression of the renin and type 1 angiotensin II receptor genes, male adult Sprague-Dawley rats were given 25 mg/kg/ day CsA s.c. for three weeks (CsA, N = 20) and were compared to pair-fed vehicle treated rats (Con, N = 20). The intrarenal distribution of renin and its mRNA was assessed by immunocytochemistry and in situ hybridization. In addition, kidney renin and type 1 angiotensin II (AT1) receptor mRNA levels were determined by Northern blot analysis. The percentage of juxtaglomerular apparatuses containing renin was higher in the CsA (84 ± 5.5{\%}) than in the Con (61 ± 6.7{\%}) group, (P < 0.05). The length of renin immunostaining along afferent arterioles was higher in the CsA (74 ± 4.5 μm) than in the Con (37 ± 5.1 μm) group, (P < 0.05). In contrast, neither renin mRNA levels nor its intrarenal distribution were altered by chronic CsA administration. Kidney AT1 receptor mRNA levels were lower in the CsA group than in the Con group. We conclude that chronic CsA: (1) induces recruitment of renin containing cells along the afferent arteriole, (2) causes no changes in intrarenal renin mRNA levels or distribution, suggesting that post-transcriptional events may be responsible for the persistence and/or uptake of renin by the preglomerular vasculature, (3) promotes a downregulation of AT1 receptor gene in the kidney, suggesting that local angiotensin II may control AT1 receptor gene expression by a negative feedback.",
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