Chapter 175 - Renal Endothelin

Abstract

Renal endothelin (ET) system plays a key role in the regulation of tubular transport and fluid-electrolyte balance. A variety of cell types in the renal cortex can produce ET-1, such as the vascular smooth muscle, glomerular endothelium, mesangial cells, and tubular epitheUal cells. Within the renal medulla, ET-1 synthesis appears to occur in the vasa recta and collecting duct cells and perhaps the thick ascending limb. Similar to the immunoreactivity studies, gene expression experiments revealed the idea that sites of ET-1 mRNA expression include the glomeruli, proximal tubules, thick ascending limbs, vasa recta, and outer and inner medullary collecting ducts and that relatively higher amounts of ET-1 are synthesized within the renal medulla. The influence of ET-1 on the renal excretion of salt and water suggested that ET-1-induced increases in renal perfusion pressure account for the natriuretic and diuretic effects of ET-1. However, at relatively low doses that do not produce decreases in glomerular infiltration rate (GFR), the systemic administration of ET-1 has been reported to have potent diuretic and natriuretic effects. In proximal tubule, ET-1 shows biphasic effect on ion transport by stimulating influx at low concentrations and inhibiting at high concentrations in which both effects are protein kinase C (PKC)-dependent.