抄録
Renal sodium handling is an essential physiologic function in mammal for body fluid maintenance. Recent advances in molecular biology have led to the identification of kidney-specific sodium transporters in the renal tubule. Urinary concentration for body fluid maintenance is accomplished by counter current multiplication in the distal tubule. Sodium transport in the thick ascending limb of Henle (TAL) is the initial process of this system. We have demonstrated that urinary concentration is regulated in part by the expression of the Na+-K+-2Cl− co-transporter (NKCC2) in TAL, by showing two mechanisms of NKCC2 expression: pitressin vasopressin (AVP)-dependent and AVP-independent mechanisms. Two additional findings, namely, a lack of the ability to increase NKCC2 in chronic renal failure or kidney isograft leads to acquired urinary concentrating defect and an enhanced NKCC2 expression (congestive heart failure and liver cirrhosis) underlies the edema-forming condition, confirm the close association between sodium handling in TAL and body fluid accumulation. We have recently demonstrated that AVP-induced alterations of NKCC2 expression are involved in the pathogenesis of hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). We have also found that Li+ entry into renal interstitium by sodium transporters including NKCC2 induces another type of acquired urinary concentrating defect in which NKCC2 expression is well conserved (lithium nephropathy; Li-N). In both SIADH and Li-N, functional blockade of NKCC2 shows the limited but significant therapeutic effects (reverse pharmacological effect of loop diuretics in Li-N). [Jpn J Physiol 55 Suppl:S36 (2005)]
