Physiologic and pathophysiologic roles of endothelin in the kidney

Endothelin is an important modulator of renal function via its binding to abundant receptors in renal tissue and by the ability of renal endothelial and epithelial cells to synthesize and release endothelin. In the kidney, endothelin may function as a paracrine-autocrine factor in the regulation of renal blood flow, glomerular hemodynamics, and sodium and water homeostasis. Recent evidence suggests that circulating endothelin may play an important role in renal regulation in cardiorenal states of endothelin activation. Endothelin is a potent renal vasconstrictor that has dual actions on glomerular filtration rate due to its ability to preferentially constrict efferent arterioles preserving glomerular filtration. Furthermore, endothelin modulates sodium excretion and water balance at the level of the proximal tubule and medullary collecting ducts, respectively, by mechanisms that are still unclear. In addition, endothelin stimulates the renin-angiotensin-aldosterone system and atrial natriuretic peptide release and inhibits arginine vasopressin-mediated water reabsorption in the inner medullary collecting duct. Recent studies using specific receptor antagonists have demonstrated a pathophysiologic role for endothelin during renal ischemia, cyclosporine-induced toxicity, and chronic renal failure. This review highlights recent research that supports an important role for endothelin as a locally produced vasoactive and natriuretic peptide in the regulation of renal hemodynamic and excretory functions.