Regulation of the abundance of renal sodium transporters and channels by vasopressin

Vasopressin plays a role in both salt and water balance in the kidney. Clas sic studies, utilizing isolated perfused tubules, have revealed that vasopr essin increases sodium reabsorption in the kidney thick ascending limb and the collecting duct. Furthermore, the activity of several sodium transport proteins expressed in these segments, such as the bumetanide-sensitive Na-K -2Cl cotransporter (NKCC2) and the epithelial sodium channel (ENaC), have b een shown to be directly increased by vasopressin. Increased protein abunda nce might be one means through which sodium transporter and channel activit y is enhanced. We have used immunoblotting and immunohistochemistry in orde r to investigate the regulation of abundance of the major sodium transporte rs and channels expressed along the renal tubule in response to vasopressin . Chronic (7-day) studies were performed in which vasopressin levels were e levated either endogenously by water restriction of Sprague-Dawley rats or exogenously through infusion of the vasopressin V2-receptor-selective agoni st, dDAVP (1-deamino-8D-arginine-vasopressin), to Brattleboro rats. We foun d a significant increase in protein abundance for NKCC2 and the beta- and g amma -subunits of ENaC with either water restriction or dDAVP infusion. The a-subunit of Na-K-ATPase was increased by water restriction, but not by dD AVP infusion, and alpha -ENaC and the thiazide-sensitive cotransporter (NCC ) were increased by dDAVP infusion but not by water restriction. Acute (60- min) in vivo exposure to dDAVP led to an increase in both beta -and gamma - ENaC abundance in kidney cortex homogenates, displaying the rapid nature of some of these changes. Overall these increases in sodium transporter and c hannel abundances likely contribute to both the antidiuretic and antinatriu retic actions of vasopressin. (C) 2001 Academic Press.