Krämer B K, Schricker K, Scholz H, Clozel M, Riegger G A, Kurtz A
Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Germany.
Kidney Int Suppl. 1996 Jun;55:S119-21.
Endothelins 1, 2, and 3 did not affect basal renin secretion, but selectively inhibited to a similar extent both cAMP-stimulated renin secretion and renin gene expression in isolated renal juxtaglomerular cells. In isolated perfused rat kidneys and after cAMP-stimulated renin secretion using isoproterenol, endothelins inhibited basal renin secretion at a perfusion pressure of 80 mm Hg. Endothelin's main action is mediated via the endothelin ETB receptor. It involves activation of phospholipase C, intracellular calcium mobilization in juxtaglomerular cells that is dependent on extracellular calcium and associated with prominent calcium-activated chloride currents, and subsequent processes. In normal rats and in rats with unilateral renal artery clips, a nonselective inhibitor of endothelin receptors, Ro 47-0203, did not significantly change renin secretion and renal renin gene expression, despite complete abolition of the vasoconstrictive and renin inhibitory action of exogenous endothelins by this drug in isolated perfused rat kidneys. In spite of a marked renin inhibitory efficacy of exogenous endothelins in vitro (isolated renal juxtaglomerular cells, isolated perfused rat kidney), endogenous endothelins play no relevant regulatory role in renin secretion and renin gene expression in normal and hypoperfused rat kidneys in vivo. However, endothelins may be of physiological relevance for the development of hypertension upon renal artery stenosis.
内皮素1、2和3不影响基础肾素分泌，但在离体肾球旁细胞中可选择性地同等程度抑制cAMP刺激的肾素分泌和肾素基因表达。在离体灌注大鼠肾脏中，以及使用异丙肾上腺素刺激cAMP分泌肾素后，内皮素在80 mmHg灌注压下抑制基础肾素分泌。内皮素的主要作用是通过内皮素ETB受体介导的。它涉及磷脂酶C的激活、球旁细胞内依赖细胞外钙的钙动员以及显著的钙激活氯电流，以及后续过程。在正常大鼠和单侧肾动脉夹闭大鼠中，内皮素受体的非选择性抑制剂Ro 47-0203并没有显著改变肾素分泌和肾脏肾素基因表达，尽管该药物在离体灌注大鼠肾脏中完全消除了外源性内皮素的血管收缩和肾素抑制作用。尽管外源性内皮素在体外（离体肾球旁细胞、离体灌注大鼠肾脏）具有显著的肾素抑制作用，但内源性内皮素在正常和灌注不足的大鼠肾脏体内肾素分泌和肾素基因表达中不发挥相关调节作用。然而，内皮素可能与肾动脉狭窄时高血压的发生具有生理相关性。
