Effect of renal interstitial adenosine infusion on phosphate excretion in diabetes mellitus rats.
We previously demonstrated an increased sensitivity of the renal vasculature to adenosine (ADO) mediated via ADO A1 receptors in streptozotocin (STZ) diabetic rats. Because ADO stimulates P(i) reabsorption in the proximal tubule, the present study was performed to determine whether the sensitivity of the renal tubular system to the antiphosphaturic effect of ADO is enhanced in STZ rats. Clearance studies were performed, and ADO was infused into the renal interstitium via implanted matrices in STZ- and control (Con) rats to mimic the effects of endogenous ADO. Renal phosphate excretion was significantly increased in STZ rats (0.75 +/- 0.05 mumol/24 h) compared with Con rats (0.35 +/- 0.08 mumol/24 h), and fractional phosphate excretion (FEPi) tended to be higher in STZ rats (34.8 +/- 4.1%) than in Con rats (26.7 +/- 2.2%). Renal interstitial ADO infusion (5 mumol/h) was significantly more antiphosphaturic in STZ rats (FEPi decreased by 2.90 +/- 1.6%; P > 0.05), in which ADO only tended to decrease FEPi. To determine the role of ADO A1 receptors on P(i) excretion, the selective ADO A1 receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was infused into the renal interstitium. DPCPX increased FEPi by 4.3 +/- 1.2% (P < 0.05) in the presence and 7.1 +/- 3.9% (P < 0.05) in the absence of ADO infusion in Con rats but had no effect on FEPi in STZ rats. In conclusion, STZ-diabetes mellitus enhances the antiphosphaturic effect of ADO by mechanisms unrelated to ADO A1 receptor stimulation.
Pflueger
A C
AC
Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Berndt
T J
TJ
Knox
F G
FG
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D017551:Microdialysis; D010710:Phosphates / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D010710:Phosphates; D014665:Vasodilator Agents; D000241:Adenosine