THE ROLE OF ANGIOTENSIN-II IN THE FEEDBACK-CONTROL OF RENIN GENE-EXPRESSION

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.