The effect of captopril treatment and its withdrawal on the gene expression of the renin-angiotensin system.
The mRNA expression of renin, angiotensinogen and angiotensin converting enzyme (ACE) was determined in the kidneys and livers from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) during chronic treatment with captopril and following its withdrawal. Chronic captopril treatment was associated with a dramatic rise in renin mRNA in the kidney and an elevation in mRNA for ACE in the liver. The release from captopril treatment was associated with a reversal of the increase in kidney renin mRNA but no reversal of the sustained elevation of ACE mRNA in the liver. In situ hybridisation revealed a localisation of renin to the area of the juxtaglomerular apparatus in the kidneys from untreated animals, but recruitment of vascular sites of renin expression in kidneys from captopril-treated animals. In kidneys from released animals, renin mRNA expression was once again confined to the juxtaglomerular apparatus. ACE mRNA was expressed in hepatocytes throughout the livers from animals in all treatment groups. The results highlight a differential effect of captopril withdrawal upon the gene expression of the components of the renin-angiotensin system in kidney and liver.
Jonsson
J R
JR
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
Frewin
D B
DB
Head
R J
RJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D002216:Captopril / Q000008:administration & dosage* / Q000009:adverse effects*; D015870:Gene Expression / Q000187:drug effects*; D015151:Immunoblotting; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000502:physiology*
D012333:RNA, Messenger; D002216:Captopril; D007703:Peptidyl-Dipeptidase A