Elucidating mechanisms underlying altered renal autoregulation in diabetes

作者：Takenaka Tsuneo^*; Inoue Tsutomu; Ohno Yoichi; Miyazaki Takashi; Nishiyama Akira; Ishii Naohito; Suzuki Hiromichi

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2012, 303(5): R495-R504.

DOI：10.1152/ajpregu.00217.2012

• adenosine
• blood pressure
• GAP junction
• renin-angiotensin system
• salt
• tubuloglomerular feedback
• Zucker rat

Takenaka T, Inoue T, Ohno Y, Miyazaki T, Nishiyama A, Ishii N, Suzuki H. Elucidating mechanisms underlying altered renal autoregulation in diabetes. Am J Physiol Regul Integr Comp Physiol 303: R495-R504, 2012. First published June 27, 2012; doi:10.1152/ajpregu.00217.2012.-Previous studies have reported that high-salt intake paradoxically activates tubuloglomerular feedback (TGF) in type 1 diabetes. Using Zucker lean (ZL) and diabetic fatty (ZDF) rats on normal and high-salt diets, renal hemodynamics and the renin-angiotensin system (RAS) were characterized. On normal salt diet, glomerular filtration rate (GFR) was higher in ZDF than ZL rats. Autoregulation of GFR was less efficient and lithium clearance was lower in ZDF rats than ZL rats. Salt load reduced GFR in ZDF rats with restoration of lithium clearance and partial improvement in autoregulatory index (AI). The administration of 8-cyclopentyl-1,3-dipropylxanthine, a selective adenosine-1 receptor antagonist to ZDF rats on a high-salt diet abolished the improvement of AI in GFR. However, this effect was seen by neither (Cx40)GAP27 nor (Cx37,43)GAP27,which inhibits connexin (Cx) 40 or Cx37. Renal ANG II was higher in ZDF than ZL rats on normal salt diet, but the difference was eliminated by a salt load. The present data provide the first demonstration for a salt paradox in type 2 diabetes and implicate that in addition to Cx alterations, an enhanced proximal reabsorption attenuates TGF, underlying glomerular hyperfiltration and RAS activation. These data suggest that a high-salt diet standardizes distal delivery in diabetes, suppressing the RAS, and improving GFR autoregulation and hyperfiltration through adenosine.

• 出版日期2012-9