Endothelins: vasoactive modulators of renal function in health and disease.

Vasoactive autocoids with directly opposing actions on the renal vasculature, glomerular function, and in salt and water homeostasis have been demonstrated in the kidney. In the renal cortex, endothelin (ET)-1 and angiotensin-II cause vasoconstriction, decreasing renal blood flow, and glomerular filtration rate, whereas bradykinin and atrial natriuretic peptide cause vasodilation and increase glomerular capillary permeability. ET-1 causes vasoconstriction of the afferent and efferent arteries and outer medullary descending vasa recta, thereby decreasing vasa recta and papillary blood flow, while bradykinin has the opposite effect. ET-1 stimulates cell proliferation, increasing the expression of several genes, including collagenase, prostaglandin endoperoxidase synthase, and platelet-derived growth factor. ET-1 promotes natriuresis via the ET-B receptor, causing down-regulation of the epithelial Na(+) channel in the renal tubule. Thus, ETs affect three major aspects of renal physiology: vascular and mesangial tone, Na(+) and water excretion, and cell proliferation and matrix formation.