ROLE OF ENDOTHELINS FOR RENIN REGULATION

Endothelins 1, 2, and 3 did not affect basal renin secretion, but sele ctively inhibited to a similar extent both cAMP-stimulated renin secre tion and renin gene expression in isolated renal juxtaglomerular cells . In isolated perfused rat kidneys and after cAMP-stimulated renin sec retion using isoproterenol, endothelins inhibited basal renin secretio n at a perfusion pressure of 80 mm Hg. Endothelin's main action is med iated via the endothelin ET(B) receptor. It involves activation of pho spholipase C, intracellular calcium mobilization in juxtaglomerular ce lls that is dependent on extracellular calcium and associated with pro minent calcium-activated chloride currents, and subsequent processes. In normal rats and in rats with unilateral renal artery clips, a nonse lective inhibitor of endothelin receptors, Ro 47-0203, did not signifi cantly change renin secretion and renal renin gene expression, despite complete abolition of the vasoconstrictive and renin inhibitory actio n of exogenous endothelins by this drug in isolated perfused rat kidne ys. In spite of a marked renin inhibitory efficacy of exogenous endoth elins in vitro (isolated renal juxtaglomerular cells, isolated perfuse d rat kidney), endogenous endothelins play no relevant regulatory role in renin secretion and renin gene expression in normal and hypoperfus ed rat kidneys in vivo. However, endothelins may be of physiological r elevance for the development of hypertension upon renal artery stenosi s.