Control of renin gene expression in 2 kidney-1 clip rats

This study was done to investigate the mechanisms that underly the changes of renal 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 reduction 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 contralateral intact kidneys. Inhibition of prostaglandin (PG) formation by meclofenamate or EDRF synthesis by L-NAME markedly attenuated the increase of renin mRNA levels in response to clipping, and a combination of PG/EDRF inhibition almost abolished the increase of renin mRNA levels. Inhibition of PG/EDRF formation did not change the suppression of renin mRNA levels in the contralateral intact kidneys. Neither did renal denervation nor inhibition of macula densa function by furosemide prevent the suppression of renin gene expression in response to unilateral renal artery clipping. Only converting enzyme inhibition by ramipril and blockade of Ang II-AT1 receptors by losartan attenuated the decrease of renin mRNA levels in the contralaterals to clipped kidneys. These findings suggest that intact PG and EDRF synthesis represent stimulatory signals for renin gene expression that are required for the elevation of renin mRNA levels upon unilateral renal hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)