CORTICOSTERONE INCREASES NA-K+-ATPASE ACTIVITY IN RAT CORTICAL COLLECTING DUCTS WITH INHIBITION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE()

To examine a physiological role of 11 beta-hydroxysteroid dehydrogenas e (11OHSD) in the aldosterone target tissues, we measured Na+-K+-ATPas e activity in the cortical collecting ducts (CCD) from adrenalectomize d rats, which were treated with a physiological dose of corticosterone and/or carbenoxolone (an inhibitor of 11OHSD). The Na+-K+-ATPase acti vity in adrenalectomized rats was not significantly changed by either corticosterone alone or carbenoxolone alone, whereas its activity show ed a significant increase only in the rats that received both corticos terone and carbenoxolone. In these rats, the plasma concentration of c orticosterone was within the physiological range (10(-6) M) and the pl asma carbenoxolone concentration was about 10(-7) M. Furthermore, the direct effect of carbenoxolone was examined in the micro dissected CCD because it has been reported that carbenoxolone per se had an affinit y for the aldosterone receptor. Na+K+-ATPase activity in the microdiss ected CCD was increased in a dose-dependent manner after a 3-hour incu bation with carbenoxolone, and this effect was completely inhibited by canrenoic acid (an aldosterone antagonist). However, the minimal carb enoxolone concentration exerting a stimulatory effect was 10(-6) M, wh ich is about 10 times higher than the plasma concentration of carbenox olone in the in vivo treated rats. These results indicate that an inhi bition of 11OHSD but not a direct action of carbenoxolone induces an i ncrease in Na+-K+-ATPase activity, which is a well-known aldosterone e ffect in the CCD.