1999 Fiscal Year Final Research Report Summary
The study on molecular biological mechanisms and therapy of sodiam and acid disturbance in renal failure
Project/Area Number |
10671000
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | Kumamoto University |
Principal Investigator |
NONOGUCHI Hiroshi University Hospital, Kumamoto University, Associate Professor, 医学部・附属病院・第三内科, 講師 (30218341)
|
Co-Investigator(Kenkyū-buntansha) |
野々口 博史 熊本大学, 医学部・附属病院・第三内科, 講師 (30218341)
|
Project Period (FY) |
1998 – 1999
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Keywords | Chronic renal failure / Vesopressin / V2 receptor / Via receptor / NKCC1 / Collecting cluct / Osmolality |
Research Abstract |
Patients with chronic renal failure showed decreased urinary excretion of sodium and acid. Several ion transporters in the kidney participate in sodium and acid excretion. We focused on secretory type Na-K-2Cl cotransporter (NKCC1). To know the role of NKCC1 in the regulation of body fluid homeostasis, we investigated the distribution of NKCC1 along the nephron in mouse and rat. NKCC1 mRNA expression was most abundant in inner medullary collecting ducts (IMCD) in mouse and outer medullary collecting ducts (OMCD) in rat. Chronic metabolic acidosis induced by the administration of NH4C1 and two-days dehydration caused a significant increases of NKCC1 mRNA expression in collecting ducts and NKCC1 protein expression in OMCD. Next, to examine the mechanisms of the up-regulation of NKCC1 mRNA expression by dehydration, the effects of hyperosmolality and vasopressin (AVP) on its expression were studied. Hyperosmolality and AVP increased NKCC1 mRNA expression in OMCD. These results show that AVP, directly or indirectly through the increase in medullary osmolality, regulates NKCC1 expression. Since V2 vasopressin receptors were downregulated in chronic renal failure, AVP plays an important role in sodium and acid excretion in patients with renal failure.
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