| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1988: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Laboratory Investigation. 1. Leukotriene D_4 (LTD_4), which stimulates superoxide, reduces renal plasma flow and glomerular filtration rate possibly by contracting mesangial cells in glomerulus. Atrial natriuretic factor (ANF), on the other hand, increases renal plasma flow and glomerular filtration rate through relaxing mesangial cell. We investigated the interaction between LTD_4 and ANF in glomerulus. ANF stimulates dose- dependently cGMP production in rat glomerulus. LTD_4 inhibited ANF-dependent cGMP production in rat glomerulus. LTD_4 possibly decreases renal function at least in part by inhibiting the production of cGMP. 2. It could not be possible to measure the amount of superoxide from the sample directly obtained through bowmann's capsule mainly because the sensitivity limits of the method. 3. Endothelin is a peptide which could be secreted from damaged endothelial cells by superoxide, and decrease renal function. This peptide is very important in the pathogenesis of ischemic acute renal failure. We investigated the interaction between endothelin and several peptides. Our results suggest that endothelin selectively inhibits AVP-dependent cAMP production in collecting ducts. Thus, endothelin will counteract the decrease in glomerular filtration rate by increasing in urine volume.
Clinical study. 1. Thyroid hormone, which probably stimulates superoxide in the kidney, was investigated in acute renal failure. Fatal group of acute renal failure has lower level of thyroid hormone, which might be regulated to decrease not to increase superoxide. 2. Endothelin, which could be secreted by damaged endothelial cells in acute renal failure, is increased in the acute stage of acute renal failure and decreased with the recovery in renal function. This results suggest some relation between endothelin and renal dysfunction in acute renal failure.
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