Renin, angiotensinogen, and kallikrein gene expression in two-kidney Goldblatt hypertensive rats.
An imbalance in the activity of the vasopressor renin-angiotensin and vasodepressor kallikrein-kinin systems may play an important role in the pathogenesis of hypertension after unilateral renal artery constriction. To test this hypothesis, we examined the expression of the renin, angiotensinogen (Ao), and tissue kallikrein genes 7 and 25 days after placement of a 0.25-mm clip on the left renal artery of rats. One week after clipping, renin mRNA levels were 4.6-fold higher in the clipped and 50% lower in the nonclipped kidneys compared with kidneys from sham-operated rats. At 25 days, renin mRNA levels in the clipped kidneys were not different from sham kidneys, but were suppressed to almost undetectable levels in the nonclipped kidneys. Steady-state Ao mRNA levels in the clipped kidneys were not different from those of nonclipped or sham kidneys at either 7 or 25 days. However, at 25 days, Ao mRNA levels were lower in the liver (70%), left ventricle (55%), and aorta (45%) of clipped than sham-operated rats. The expression of the renal kallikrein gene was unchanged at 7 days and was suppressed by 50% at 25 days. These results are consistent with the notion that activation of the intrarenal renin-angiotensin system occurs during the initial phase of the two-kidney, one-clip hypertension model. The renal kallikrein gene, in marked contrast to renin, becomes downregulated in the chronic phase. The differential regulation of renin-angiotensin and kallikrein genes may be an important pathogenetic factor in renovascular hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
el-Dahr
S S
SS
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Dipp
S
S
Guan
S
S
Navar
L G
LG
D000808:Angiotensinogen / Q000032:analysis / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D004247:DNA / Q000032:analysis / Q000235:genetics; D015536:Down-Regulation; D015870:Gene Expression / Q000235:genetics*; D006978:Hypertension, Renovascular / Q000235:genetics*; D007610:Kallikreins / Q000032:analysis / Q000235:genetics*; D007668:Kidney / Q000737:chemistry; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000032:analysis / Q000235:genetics*; D013997:Time Factors
D012333:RNA, Messenger; D000808:Angiotensinogen; D004247:DNA; D007610:Kallikreins; D012083:Renin