New Treatment for Nephropathy with the Normalization of Tubulo-Glomerular Feedback Mechanisms

它是speculated an abnormal tubulo-glomerular feedback (TGF) activity may induce thenephropathy via renal hemodynamic changes. However，there are no useful technique to evaluate the TGF activity. In addition，the transmitters from macula densa cells to afferent arterioles have been determined yet. Wefortunately solved the first problem by introducing the in vivo dynamic method to evaluate TGFactivity . so,the purposes of this project are to determine the transmitter in TGF mechanisms and to develop the新策略for the treatment of nephropathy by the normalization of TGF activity.1.Determinationmediators in TGF mechanisms：The renal interstitial concentration of adenosine，ATP和NO metabolites.我们观察TGF-mediated changes in renal的positive correlationvascular resistance and renal interstitial concentration of ATP. Thus，2.TGF activity in Dahl salt -sensitive （DS）我们可以采取行动，提高ATP for the candidate of TGF mediator.2rats: DS rars were…More intained on low(L:0.3% NaCl) or high salt(H:8% NaCl) diets for 4 weeks. Using in vivo动态方法描述above，ficial afferent arteriolar diameter (AAD) was measured before and during enhanced TGF activityinduced by acetazolamide(ACZ). Compared to DS L rats，DS H rats showed smaller basal AAD. ACZ significantly decreased, AAD in DS L rats，but did not change AAD in DS·H rats. Furosemide increased AADs in both rats. These findings indicatean enhancement of TGF activity in DS H rats.3.Effect of P2 receptor antagonist, suramin，on TGF activity in DS / H rats：Treatment of suramin significantly increased basal AADbut AAD did not change during administration of ACD and furosemide，indicating suramin normalized the enhanced TGF activity in DS·H rats.4.Effects of suramin on bloodpressure and urinary excretion of protein：Suramin markedly attenuated the development of hypertension and decreased the urinary proteinexcretion in DS . H rates . the result indicates that the development of nephropathy and hypertension isassociated with an enhancement of TGF activity in DS H rats. P2 receptor antagonist应该是一个良好的agent for the treatment of nephropathy. Less

It is speculated that an abnormal tubulo-glomerular feedback (TGF) activity may induce the nephropathy via renal hemodynamic changes. However, there are no useful technique to evaluate the TGF activity. In addition, the transmitters from macula densa cells to afferent arterioles have not been determined yet. We have fortunately solved the first problem by introducing the in vivo dynamic method to evaluate TGF activity. So, the purposes of this project are to determine the transmitter in TGF mechanisms and to develop the new strategy for the treatment of nephropathy by the normalization of TGF activity.1.Determination of mediators in TGF mechanisms : The renal interstitial concentration of adenosine, ATP and NO metabolites. We observed the positive correlation between TGF-mediated changes in renal vascular resistance and renal interstitial concentration of ATP. Thus, we could pick up ATP for the candidate of TGF mediator.2.TGF activity in Dahl salt -sensitive (DS) rats : DS rars were ma … More intained on low(L:0.3% NaCl) or high salt(H:8% NaCl) diets for 4 weeks. Using in vivo dynamic method described above, superficial afferent arteriolar diameter (AAD) was measured before and during enhanced TGF activity induced by acetazolamide(ACZ). Compared to DS・L rats, DS・H rats showed smaller basal AAD. ACZ significantly decreased, AAD in DS・L rats, but did not change AAD in DS・H rats. Furosemide increased AADs in both rats. These findings indicate an enhancement of TGF activity in DS・H rats.3.Effect of P2 receptor antagonist, suramin, on TGF activity in DS・H rats : Treatment of suramin significantly increased basal AAD, but AAD did not change during administration of ACD and furosemide, indicating suramin normalized the enhanced TGF activity in DS・H rats.4.Effects of suramin on blood pressure and urinary excretion of protein : Suramin markedly attenuated the development of hypertension and decreased the urinary protein excretion in DS・H rats.The result indicates that the development of nephropathy and hypertension is associated with an enhancement of TGF activity in DS・H rats. P2 receptor antagonist should be a good agent for the treatment of nephropathy. Less