Modulation of renin-angiotensin and kallikrein gene expression in experimental hypertension.
Previous studies have shown that chronic low-dose administration of 40 ng/min angiotensin II by osmotic minipump to uninephrectomized rats mimics the temporal hypertensive response and the circulating angiotensin II levels observed in two-kidney, one clip Goldblatt rats. Furthermore, renal tissue angiotensin II contents were higher than the circulating angiotensin II levels, suggesting that circulating angiotensin II induces endogenous intrarenal angiotensin II production. The present study examined the molecular mechanisms by which intrarenal angiotensin II production is modulated in angiotensin II-induced and two-kidney Goldblatt hypertension. Two weeks after clipping, intrarenal renin mRNA levels were elevated threefold in the clipped kidney of Goldblatt rats but were markedly suppressed in the nonclipped kidneys of Goldblatt rats (28% of control values) and in the remaining kidney of uninephrectomized angiotensin II-infused rats (7% of control values). In contrast, there were sustained levels of angiotensinogen mRNA in the kidneys and livers of Goldblatt and angiotensin II-infused rats, indicating differential regulation of the genes of the renin-angiotensin system. Renal kallikrein gene expression was not altered in either of the hypertensive groups 14 days after the induction of hypertension, suggesting the absence of an enhanced counteracting kinin influence.
Von Thun
A M
AM
Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112.
el-Dahr
S S
SS
Vari
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RC
Navar
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LG
D000804:Angiotensin II / Q000096:biosynthesis* / Q000097:blood; D000808:Angiotensinogen / Q000096:biosynthesis*; D000818:Animals; D001794:Blood Pressure; D015152:Blotting, Northern; D005786:Gene Expression Regulation; D006978:Hypertension, Renovascular / Q000378:metabolism* / Q000503:physiopathology; D007610:Kallikreins / Q000096:biosynthesis*; D007668:Kidney / Q000201:enzymology*; D008297:Male; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000096:biosynthesis* / Q000097:blood; D012084:Renin-Angiotensin System
D012333:RNA, Messenger; D000808:Angiotensinogen; D000804:Angiotensin II; D012313:RNA; D007610:Kallikreins; D012083:Renin