title: Elucidating mechanisms underlying altered renal autoregulation in diabetes.
abstract: 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.
authors: Department of Nephrology and Community Health Science Center, Saitama Medical University, Iruma Saitama 350-0495 Japan. takenaka@saitama-med.ac.jp
authors: Tsuneo
authors: T
authors: Takenaka
authors: Tsutomu
authors: T
authors: Inoue
authors: Yoichi
authors: Y
authors: Ohno
authors: Takashi
authors: T
authors: Miyazaki
authors: Akira
authors: A
authors: Nishiyama
authors: Naohito
authors: N
authors: Ishii
authors: Hiromichi
authors: H
authors: Suzuki
mesh_terms: D000818:Animals; D017630:Connexins / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D017630:Connexins; D058915:Purinergic P1 Receptor Antagonists; D017673:Sodium Chloride, Dietary; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine