Renin and angiotensinogen gene expression and intrarenal renin distribution during ACE inhibition.
To define whether intrarenal renin and angiotensinogen synthesis and distribution are affected by angiotensin-converting enzyme (ACE) inhibition, a control group of adult, male Wistar-Kyoto rats (n = 7) was compared with a group of rats treated with enalapril (n = 8) for 5 days. Kidney renin and angiotensinogen mRNA levels were detected by Northern and dot blot analysis, using full-length rat renin and angiotensinogen cDNAs. Renin mRNA levels in the enalapril-treated group were 4.6-fold higher than in the control group (P less than 0.05). Angiotensinogen mRNA levels were not significantly different. The intrarenal distribution of renin assessed by immunocytochemistry was markedly different between the two groups of rats. Whereas in the control kidney renin was localized in a juxtaglomerular position, in the kidneys from enalapril-treated rats, renin immunoreactivity of the afferent arteriole extended well beyond the juxtaglomerular loci in the direction of the interlobular artery. The percent of afferent arteriolar length immunostained for renin was higher in the enalapril-treated (53 +/- 17%) than in the control (33 +/- 15) group. Similarly, the ratio of immunostained juxtaglomerular apparatuses (JGA) over total number of JGA and the ratio of immunostained arteries over total number of arteries were higher in the enalapril-treated (0.84 +/- 0.017; 0.68 +/- 0.03) than in the control (0.67 +/- 0.034; 0.43 +/- 0.045) group (P less than 0.05). We conclude that chronic ACE inhibition enhances intrarenal renin synthesis and increases renin expression upstream from the glomerulus and in new sites in blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Gomez
R A
RA
Department of Pediatrics, School of Medicine, University of Virginia, Charlottesville 22908.
Lynch
K R
KR
Chevalier
R L
RL
Everett
A D
AD
Johns
D W
DW
Wilfong
N
N
Peach
M J
MJ
Carey
R M
RM
D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D004247:DNA / Q000235:genetics; D004656:Enalapril / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005796:Genes; D007606:Juxtaglomerular Apparatus / Q000187:drug effects / Q000201:enzymology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D051381:Rats; D011921:Rats, Inbred WKY; D012016:Reference Values; D012083:Renin / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D000808:Angiotensinogen; D004656:Enalapril; D004247:DNA; D012083:Renin