| Budget Amount *help |
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
High-salt diet initiates and accelerates both hypertension and renal injury in Dahl salt-sensitive (DS), but not in salt-resistant (DR), rats. Impaired renal autoregulation, including myogenic response, shown in DS rats on high-salt diet suggests impaired another autoregulatory mechanism, tubuloglomerular feedback (TGF). However, TGF responsiveness has been reported to be normal on high-salt diet or even blunted during low-salt diet. Thus, our purpose is to determine the functional state of the TGF mechanism in Dahl rats. Clearance and micropucture experiments were performed in anesthetized DS and DR rats on 0.4 % (NS) or 4 % NaCl (HS) diet for 1-4 weeks. TGF responsiveness was assessed in superficial nephrons by measuring the changes of early proximal flow rate (EPFR), an index of single nephron GFR, in response to orthograde loop perfusion at 40-60 nl/min with artificial tubular fluid. In DS rats, HS diet increased systemic BP, GFR, EPFR at zero loop perfusion, proteinuria, and kidney weight more than NS diet, while body weight was comparable between two diets. The reductions of EPFR by loop perfusion at 60 nl/min were significantly less on HS than NS diet, indicating TGF attenuation on HS diet. In DR rats, HS diet did not induce proteinuria and EPFR reductions were comparable between two diets. Microperfusion of NO synthase inhibitor, nitro-L-arginine 10^<-3>M, into loop of Henle enhanced TGF responsiveness in DS rats on NS diet more than on HS diet. Administration of vasopeptidase inhibitor, BMS-186716 (4 mg/kg i.v.) did not affect TGF responsiveness. In conclusion, in DS rats, HS diet clearly attenuated TGF and induced glomerular hyperfiltration in single nephron level. Glomerular hyperfiltration, or possibly glomerular hypertension through TGF dysfunction, may underlie HS diet-induced proteinuria and renal injury. In DR rats, HS diet did not depress TGF responsiveness.
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