| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
The mechanisms protecting against or promoting the development of diabetic nephropathy are still not well understood. Studies were performed in type 2 diabetic rats to investigate existence and time point of onset of renal hemodynamic abnormalities. In 12 week old type 2 diabetic rats (OLETF), considered to be prediabetic, and control rats (LETO) we determined the effect of the AT1 receptor antagonist olmesartan (OLM; 5mg/kg) on total (RBF), superficial (SBF), and deep renal cortical blood flow (DBF). SBF was significantly increased by OLM in LETO, but not in OLETF. In contrast, OLM had no effect on DBF in LETO, but increased DBF in OLETF. Micropuncture studies showed that tubuloglomerular feedback (TGF) responses were reduced in OLETF (7.3 v.s 25.7%). In OLETF at about 40 weeks of age and LETO of comparable age we assessed the effect of comparable reductions of renal perfusion pressure (RPP) induced by clamping the abdominal aorta on RBF, SBF and DBF. Whereas SBF showed no significant change in both OLETF and LETO rats, DBF decreased significantly more in OLETF than LETO. TGF responses were reduced in OLETF (4.4 v.s. 18.8%). Renal corticotomy was performed to measure glomerular capillary pressure (P_<gc>). P_<gc> in OLETF was significantly higher in deep than superficial nephrons (78±2 v.s. 57±4 mm Hg). These findings strongly suggest the presence of abnormal renal hemodynamics, especially in the deep cortical region, in type 2 diabetes ; OLM may improve these abnormalities at the prediabetic stage.
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