| Co-Investigator(Kenkyū-buntansha) |
AMEMIYA Morimasa Jichi Medical School, Dept Nephrol, Instructor, 医学部, 助手 (90275678)
KAWAKAMI Kiyoshi Jichi Medical School, Dept Biol, Professor, 医学部, 教授 (10161283)
MUTO Shigeaki Jichi Medical School, Dept Nephrol, Assistant Professor, 医学部, 講師 (40190855)
ONO Shuichi Jichi Medical School, Dept Nephrol, Instructor, 医学部, 助手 (90285776)
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| Research Abstract |
We used cultured vascular smooth muscle cells (VSMC) and kidney cells to determine the roles of Na-transporters (Na pump, Na/H exchanger, and epithelial Na channel) in the disorders of salt balance. The results were in the following:
1) In VSMC, serum, hyperosmolality (induced by mannitol and glucose), corticosterone and its metabolite, 11-dehydrocorticosterone, differentially stimulated Na pump αl-and β1-mRNA expression, α- and β1-subunit protein expression, and Na, K-ATPase activity; 2) Low Na diet (elevated endogenous aldosterone levels) increased epithelial Na channel α subunit mRNA levels from inner medulla of the rat kidneys, but did not affect β or γ subunit mRNA levels; 3) In the rabbit cortical collecting duct (CCD), acute elevation of basolateral K concentrations from 2.5 to 8.5 mM activated the basolateral Na pump, which secondarily elevates the apical Na and K conductances. DOCA pretreatment increased the basolateral K conductances and augmented the response to the rise of K of both the basolateral Na pump activity and the apical cation conductances. Luminal Na concentration, probably by changes in cell Na concentrations, modulated the tight coupling between the basolateral Na pump and apical cation conductances; 4) In the CCD from control rabbits, raising luminal Na concentrations from 14 to 147 mM activated basolateral Na pump and apical Na and K conductances via increased cell Na concentration. The luminal Na-dependent activation of the basolateral pump and the apical cation conductances was sharply enhanced in the CCD from DOCA-treated rabbits. Chronic DOCA pretreatment also increased basolateral K conductance upon raising luminal Na concentration; 5) In VSMC, aldosterone activated Na/H exchange (NHE) by nongenomic and genomic mechanisms; 6) Incubation of OKP cells in low-K media increased NHE3 activity after early decrease in intracellular PH; and 7) Extracellular Cl modulated shrinkage-induced activation of NHE in rat renal mesangial cells.
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