Role of endothelins for renin regulation.

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.