Moe O, Tejedor A, Campbell W B, Alpern R J, Henrich W L
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Am J Physiol. 1991 Apr;260(4 Pt 1):E521-5. doi: 10.1152/ajpendo.1991.260.4.E521.
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)
内皮素-1（ET-1）在存在肾素刺激剂的情况下直接抑制肾素分泌的能力尚不清楚，任何肾素抑制作用的机制也是如此。因此，在两种不同的制剂中研究了ET-1对肾素分泌的直接影响：大鼠肾皮质切片和分离的肾小球旁细胞（JGC）。在大鼠肾皮质切片中，ET-1在10^(-9)和10^(-8) M时分别使基础肾素释放降低20%（P<0.05）和44%（P<0.005）。为了测试ET-1作为肾素抑制剂的功效，在肾素刺激剂异丙肾上腺素（10^(-5) M）存在的情况下进行了实验。向皮质切片中添加异丙肾上腺素可使肾素释放增加97%（P<0.001）；ET-1（10^(-8) M）将异丙肾上腺素引起的肾素释放增加限制了80%（P<0.05）。在JGC中观察到类似的效果，因为ET-1（10^(-8) M）使基础肾素分泌显著降低26%（P<0.05）。在分离的JGC中，异丙肾上腺素使肾素分泌增加151%（P<0.001）；ET-1（10^(-8) M）使这种刺激引起的肾素分泌增加显著降低68%。通过测试细胞内钙缓冲剂1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸（BAPTA；10^(-6) M）在JGC中的作用来研究肾素抑制的机制。单独使用BAPTA可使JGC中的肾素分泌增加116%（P<0.01）；当在JGC中测试（10^(-6) M）BAPTA和ET-1（10^(-8) M）的组合时，肾素分泌仍显著增加（增加78%，P<0.05）。（摘要截短至250字）
