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1 Institut fur Physiologie, Universitat Regensburg, Regensburg, Germany
* To whom correspondence should be addressed. E-mail: juergen.klar{at}vkl.uni-regensburg.de.
The secretion and the synthesis of renin as the key regulator of the renin-angiotensinaldosterone system are directly controlled by angiotensin II in the sense of a negative feedback. Since we found that renal afferent arterioles including the juxtaglomerular portion express the mineralocorticoid receptor, we aimed to characterize a possible direct effect of aldosterone on renin synthesis and renin secretion at the level of renal juxtaglomerular cells. Aldosterone (100nM) clearly enhanced renin mRNA levels in primary cultures of mouse juxtaglomerular cells prestimulated with isoproterenol (100 nM), but had no effect on the exocytosis of stored renin. Similarly, in the mouse juxtaglomerular cell line As4.1 aldosterone time and concentration dependently increased renin mRNA abundance and prorenin secretion up to 2.5-fold. Moreover, aldosterone potentiated cAMP induced renin gene expression in As4.1 cells. The effect of aldosterone was inhibited by spironolactone and was mimicked by corticosteroid hormones but not by sex steroids. Aldosterone had no influence on basal renin promoter activity but increased the renin mRNA half-life about 3-fold. In summary, these data suggest that aldosterone exerts a direct positive effect on renin gene expression at the cellular level probably by stabilizing renin mRNA.
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