This study aimed to characterize the influence of endogenous angiotens
in II on renal renin gene expression during different states of a stim
ulated and of a suppressed renin system. To this end the renin system
in male Sprague Dawley rats was stimulated by unilateral renal artery
clipping (0.2 mm clip), by furosemide (60 mg/kg per diem) or isoproter
enol (160 mu g/kg per diem), and by ingestion of a low-salt diet (0.02
%), or was suppressed by setting a contralateral renal artery clip (0.
2-mm clip) or by ingestion of a high-salt diet (4%). During the last 2
days of these different treatment regimens, the animals were treated
with the angiotensin II ATI receptor antagonist losartan (40 mg/kg per
diem) and renal renin mRNA levels were assayed. Renin gene expression
was stimulated four- to fivefold by renal artery clipping and isoprot
erenol infusion. two- to three-fold by furosemide and a low-salt diet,
and about four-fold by losartan. Additional treatment with losartan p
otentiated the stimulatory effects of a low-salt diet, of furosemide a
nd of isoproterenol infusion on renin gene expression, whilst there wa
s no significant additional effect of losartan on renin gene expressio
n in clipped kidneys. Both contralateral renal artery clipping and a h
igh-salt diet decreased renin mRNA levels to about 50% of the control
value. In rats with a unilateral clip. additional losartan treatment c
aused renin mRNA to increase to about 350% of the control value in the
contralateral kidney but to only 110% of the control value in animals
on a high-salt diet. These findings suggest that the enhanced formati
on of angiotensin II during a low-sail intake, during tubular inhibiti
on of salt reabsorption or during beta-adrenoreceptor activation plays
a relevant negative feedback role in the activation of the renin gene
. Moreover, in rats with one hypoperfused kidney, angiotensin II could
be involved in the inhibition of renin gene expression in the contral
ateral kidney. In hypoperfused kidneys, however, and in animals on a h
igh-salt diet, angiotensin II appears to play only a minor feedback ro
le in the regulation of the renin gene.