• Mitsunobu Matsubara.
• Department of Molecular Medicine and Gene Transfer Research, Tohoku University School of Medicine and Pharmaceutical Siences, Sendai, Japan. mmitsu2i@mail.tains.tohoku.ac.jp
• Yakugaku Zasshi. 2004 Jun 1; 124 (6): 301-9.

AbstractRenal sodium handling is an essential physiologic function in mammal for body fluid maintenance and blood pressure regulation. Recent advances in molecular biology have led to the identification of kidney-specific sodium transporters in the renal tubule, thereby supplying vast information for renal physiology as well as systemic physiology. Renal 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 renal urinary concentration is regulated in part by the expression of the Na(+)-K(+)-2Cl(-) co-transporter (BSC1) in TAL, by showing two mechanisms of BSC1 expression: pitressin vasopressin (AVP)-dependent and AVP-independent mechanisms. Two additional findings, namely, a lack of the ability to increase BSC1 expression leads to urinary concentrating defect and an enhanced BSC1 expression underlies the edema-forming condition, confirm the close association between sodium handling in TAL and body fluid accumulation. The lines of evidence from our genetic studies of the general Japanese population suggest the importance of mendelian hypertension genes in the genetic investigation of essential hypertension. Because those genes directly or indirectly regulate sodium transport by the Na-Cl co-transporter or the epithelial sodium channel in the distal convoluted tubule to the collecting duct (distal tubular segments after TAL), sodium handling in this part of the renal tubule may be, at least in part, involved in blood pressure regulation. The unveiling of such physiologic roles of sodium handling based on the sodium transporters or on the tubular segments may lead to a better understanding of systemic physiology as well as to the development of novel therapy for body fluid or blood pressure disorders.

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