Angiotensin-converting enzyme inhibition alters clusterin mRNA expression in the kidney following renal mass reduction.
The effect of the angiotensin-converting enzyme inhibitor captopril on clusterin mRNA was examined in partially nephrectomized male rats. Urine protein excretion was measured 3, 7, and 28 days after removal of five sixths of the renal mass. Nephrectomy caused a progressive increase in clusterin mRNA levels in the remnant kidney. Maximal clusterin mRNA levels occurred 7 days after nephrectomy and declined 28 days after nephrectomy. Captopril, 250 mg/ml in drinking water, prevented the injury-induced increase in clusterin mRNA at 7 and 28 days. Captopril had no effect on clusterin in sham-operated rats. As expected, the urine protein excretion increased progressively after nephrectomy, and this was attenuated by administration of captopril in the drinking water. Therefore, clusterin is a marker of renal injury which, along with proteinuria, is modulated by angiotensin-converting enzyme inhibition.
Olson
B A
BA
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19416, USA.
Ali
S M
SM
Contino
L C
LC
Brooks
D P
DP
Laping
N J
NJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D002216:Captopril / Q000494:pharmacology*; D051152:Clusterin; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006023:Glycoproteins / Q000187:drug effects* / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D008297:Male; D018832:Molecular Chaperones; D009392:Nephrectomy; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects; D011507:Proteinuria / Q000652:urine; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D002216:Captopril; D007703:Peptidyl-Dipeptidase A