TY - JOUR
T1 - Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney
AU - Tufro-Mcreddie, Alda
AU - Gomez, R. Ariel
AU - Norling, Laura L.
AU - Omar, Alaaedin A.
AU - Moore, Leon C.
AU - Kaskel, Frederick J.
N1 - Funding Information:
This work was performed during Dr. Kaskel's sabbatical leave in Dr. Gomez's laboratory (University of Virginia School of Medicine). The authors deeply appreciate the technical assistance of Diane Beaudoin, Aija Birzgalis (SUNY/Stony Brook), Doris Hannum, Ginny Ragsdale and Neysa Wilfong (UVA). Dr. Tufro-McReddie is supported by the Marion Hypertension research award and American Heart Association Virginia affiliate (91-F-62) fellowship training grant. Dr. Gomez is supported by NIH grants 41899 and HL02307. Dr. Kaskel is supported by a grant from the Juvenile Diabetes Foundation and Dr. Moore is supported by NIH DK26341. Sandimmune was a gift from Sandoz Pharmaceuticals, Inc.
PY - 1993/3
Y1 - 1993/3
N2 - 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.
AB - 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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U2 - 10.1038/ki.1993.90
DO - 10.1038/ki.1993.90
M3 - Article
C2 - 8455360
AN - SCOPUS:0027532594
SN - 0085-2538
VL - 43
SP - 615
EP - 622
JO - Kidney international
JF - Kidney international
IS - 3
ER -