Opposite feedback control of renin and aldosterone biosynthesis in the adrenal cortex by angiotensin II AT1-subtype receptors.
The aims of this study were to identify whether tissue renin is regulated by a negative-feedback mechanism produced by locally generated angiotensin (Ang II) in the adrenal cortex and to detect the pathway of Ang II modulation. For this purpose, in 36 12-week old, salt-restricted, nephrectomized Sprague-Dawley rats, we studied the effects of the Ang II AT1-subtype receptor antagonist losartan and of the Ang II AT2-subtype receptor antagonist PD123319 on renin mRNA and activity, aldosterone synthase mRNA, and AT1a-, AT1b-, and AT2-subtype receptor expression in the adrenal cortex. Ten additional rats, kept on a regular diet and then nephrectomized, were also studied. In salt-restricted, nephrectomized rats, losartan administration caused increases of adrenal renin mRNA (P<.05) and activity (P<.05) and a concomitant reduction of aldosterone synthase mRNA (P<.05). In addition, after losartan AT1b, receptor mRNA was reduced (P<.05), AT1a receptor mRNA was unchanged, and AT2 mRNA was increased (P<.05). PD123319 did not significantly modify any of these parameters. In conclusion, in salt-restricted, nephrectomized rats, selective antagonism of AT1-subtype receptors stimulates the expression and the activity of renin in the adrenal cortex. This observation demonstrates that Ang II locally formed in the adrenal cortex exerts a modulatory negative-feedback action on adrenal renin biosynthesis independent of the influence of the circulating renin-Ang system; this action is largely mediated through the AT1b-subtype receptors.
Gigante
B
B
Department of Internal Medicine Federico II University Naples, Italy.
Rubattu
S
S
Russo
R
R
Porcellini
A
A
Enea
I
I
De Paolis
P
P
Savoia
C
C
Natale
A
A
Piras
O
O
Volpe
M
M
D000302:Adrenal Cortex / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D005246:Feedback; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000145:classification / Q000235:genetics / Q000502:physiology*; D012083:Renin / Q000096:biosynthesis*; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C073402:PD 123319; D000450:Aldosterone; D012083:Renin; D019808:Losartan