Regulation of aldosterone biosynthesis by adrenal renin is mediated through AT1 receptors in renin transgenic rats.
The transgenic (TG) rat (mREN2)27 is characterized by overexpression of the additional mouse Ren-2d gene in the adrenal cortex with marked suppression of renal renin. We have previously shown that in salt-depleted TG rats enhanced activation of mineralocorticoid biosynthesis is associated with selective stimulation of adrenal renin. To investigate whether the local renin-angiotensin system regulates aldosterone biosynthesis in the adrenal cortex of TG rats, we studied the effects of the AT1-angiotensin subtype receptor antagonist DuP 753 on aldosterone production in 5-week-old TG rats during salt restriction. All the rats (n = 56) were shifted from regular chow to a diet containing only 0.04% NaCl for 1 week. The AT1-receptor antagonist DuP 753 (10 mg/kg per day in drinking water) was administered to 27 of these rats during low-salt diet. Subgroups of rats were killed at 0,4, and 7 days. Low-salt diet increased both adrenal renin activity (from 31 +/- 3 to 77 +/- 4 and 85 +/- 2 ng angiotensin I.h-1.mg protein-1 at 4 and 7 days, respectively; P < .001) and mRNA (by 68.4 +/- 10% and 80 +/- 17% from baseline, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Volpe
M
M
Department of Internal Medicine, School of Medicine, Federico II University, Napoli, Italy.
Rubattu
S
S
Gigante
B
B
Ganten
D
D
Porcellini
A
A
Russo
R
R
Romano
M
M
Enea
I
I
Lee
M A
MA
Trimarco
B
B
D000302:Adrenal Cortex / Q000737:chemistry* / Q000201:enzymology; D000450:Aldosterone / Q000096:biosynthesis*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D015152:Blotting, Northern; D004039:Diet, Sodium-Restricted; D015971:Gene Expression Regulation, Enzymologic; D007093:Imidazoles / Q000494:pharmacology; D007672:Kidney Cortex / Q000737:chemistry; D019808:Losartan; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology*; D012083:Renin / Q000032:analysis / Q000097:blood / Q000235:genetics* / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; D012083:Renin; D019808:Losartan