Effects of endothelin on in vitro renin secretion

The ability of endothelin-1 (ET-1) to directly inhibit renal renin secretion in the presence of a renin stimulator is unknown, as is the mechanism of action of any renin inhibition. Thus direct effects of ET-1 on renin secretion were investigated in two distinct preparations: rat kidney cortical slices and isolated juxtaglomerular cells (JGC). In rat kidney cortical slices, ET-1 reduced basal renin release by 20 (P less than 0.05) and 44% (P less than 0.005) at 10(-9) and 10(-8) M, respectively. To test the efficacy of ET-1 as a renin inhibitor, experiments were performed in the presence of the renin stimulator isoproterenol (10(-5) M). Addition of isoproterenol to cortical slices increased renin release by 97% (P less than 0.001); ET-1 (10(-8) M) limited this increase in renin release by isoproterenol by 80% (P less than 0.05). Similar effects were observed in JGC as ET-1 (10(-8) M) significantly reduced basal renin secretion by 26% (P less than 0.05). In isolated JGC, isoproterenol increased renin secretion by 151% (P less than 0.001); ET-1 (10(-8) M) significantly reduced this stimulated increase in renin secretion by 68%. The mechanism of renin inhibition was examined by testing the effects of the intracellular calcium buffer 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA; 10(-6) M) in JGC. BAPTA alone increased renin secretion in JGC by 116% (P less than 0.01); when the combination of (10(-6) M) BAPTA and ET-1 (10(-8) M) were tested in the JGC, renin secretion still increased significantly (by 78%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)