CONTROL OF RENIN GENE-EXPRESSION IN 2-KIDNEY 1-CLIP RATS

Control of renin gene expression in 2 kidney-1 clip rats. This study w as done to investigate the mechanisms that underly the changes of rena l renin gene expression upon hypoperfusion of one kidney. To this end the left renal arteries of male Sprague-Dawley rats were clipped with 0.2 mm silver clips and renal renin mRNA levels were assayed by RNase protection during the first ten days after clipping. Unilateral reduct ion of renal blood flow led to transient maximal fivefold increases of renin mRNA levels in the clipped kidneys and to sustained suppression of renin gene expression to 20% of the control value in the contralat eral intact kidneys. Inhibition of prostaglandin (PG) formation by mec lofenamate or EDRF synthesis by L-NAME markedly attenuated the increas e of renin mRNA levels in response to clipping, and a combination of P G/EDRF inhibition almost abolished the increase of renin mRNA levels. Inhibition of PG/EDRF formation did not change the suppression of reni n mRNA levels in the contralateral intact kidneys. Neither did renal d enervation nor inhibition of macula densa function by furosemide preve nt the suppression of renin gene expression in response to unilateral renal artery clipping. Only converting enzyme inhibition by ramipril a nd blockade of Ang II-AT, receptors by losartan attenuated the decreas e of renin mRNA levels in the contralaterals to clipped kidneys. These findings suggest that intact PG and EDRF synthesis represent stimulat ory signals for renin gene expression that are required for the elevat ion of renin mRNA levels upon unilateral renal hypoperfusion. The supp ression of the renin gene in the intact contralateral kidney appears t o require the presence of Ang II but seems not to be regulated by this parameter, suggesting the existence of an as yet unidentified factor that acts in concert with Ang II to suppress renin gene expression.