Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney.
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 microns) than in the Con (37 +/- 5.1 microns) 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.
Tufro-McReddie
A
A
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville.
Gomez
R A
RA
Norling
L L
LL
Omar
A A
AA
Moore
L C
LC
Kaskel
F J
FJ
D000818:Animals; D001483:Base Sequence; D016572:Cyclosporine / Q000494:pharmacology*; D004247:DNA / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D016572:Cyclosporine; D004247:DNA; D012083:Renin