ROLE OF THE MACULA DENSA IN THE CONTROL OF RENAL RENIN GENE-EXPRESSION IN 2-KIDNEY ONE-CLIP RATS

This study was designed to examine whether macula densa function is in volved in the changes or renal renin gene expression upon acute hypope rfusion of one kidney. To block macula densa function, rats with free access to salt and water were subcutaneously infused with furosemide ( 12 mg/day) for 6 days. Then, 4 days after the start of the infusion, t he left renal arteries were clipped with 0.2-mm silver clips and renin mRNA levels in ipsilateral and contralateral kidneys, as well as plas ma renin activities (PRA), were determined 48 h after clipping. In non -clipped animals furosemide increased PRA from 10 to 47 ng angiotensin I.h(-1).ml(-1) and raised renin mRNA levels in both kidneys 2.5-fold. In vehicle-infused animals, clipping of the left renal artery increas ed PRA to 37 ng angiotensin I.h(-1).ml(-1) and led to a 5-fold rise of renin mRNA levels in the ipsilateral kidneys and to a suppression to 20% of the control values in the contralateral kidneys. PRA values in clipped and furosemide-infused animals were 45 ng angiotensin I.h(-1). ml(-1). In these animals renin mRNA levels increased in the ipsilatera l kidneys to similar absolute values as in vehicle-infused rats, whils t contralateral renin mRNA levels fell to about 25% of the respective controls. These findings indicate that the stimulations of renin gene expression by inhibition of macula densa salt transport and by renal a rtery clipping are not additive, suggesting that the macula densa mech anism may participate in the stimulation of renin gene expression upon hypoperfusion. The macula densa mechanism, however, appears to be not essentially involved in the suppression of renin gene expression in t he contralaterals to stenosed kidneys.