Angiotensin II contributes to glomerular hyperfiltration in diabetic rats independently of adenosine type I receptors

Am J Physiol Renal Physiol. 2013 Mar 1;304(5):F614-22. doi: 10.1152/ajprenal.00285.2012. Epub 2013 Jan 2.

Abstract

Increased angiotensin II (ANG II) or adenosine can potentiate each other in the regulation of renal hemodynamics and tubular function. Diabetes is characterized by hyperfiltration, yet the roles of ANG II and adenosine receptors for controlling baseline renal blood flow (RBF) or tubular Na(+) handling in diabetes is presently unknown. Accordingly, the changes in their functions were investigated in control and 2-wk streptozotocin-diabetic rats after intrarenal infusion of the ANG II AT1 receptor antagonist candesartan, the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or their combination. Compared with controls, the baseline blood pressure, RBF, and renal vascular resistance (RVR) were similar in diabetics, whereas the glomerular filtration rate (GFR) and filtration fraction (FF) were increased. Candesartan, DPCPX, or the combination increased RBF and decreased RVR similarly in all groups. In controls, the GFR was increased by DPCPX, but in diabetics, it was decreased by candesartan. The FF was decreased by candesartan and DPCPX, independently. DPCPX caused the most pronounced increase in fractional Na(+) excretion in both controls and diabetics, whereas candesartan or the combination only affected fractional Li(+) excretion in diabetics. These results suggest that RBF, via a unifying mechanism, and tubular function are under strict tonic control of both ANG II and adenosine in both control and diabetic kidneys. Furthermore, increased vascular AT1 receptor activity is a contribution to diabetes-induced hyperfiltration independent of any effect of adenosine A1 receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A1 Receptor Antagonists / pharmacology
  • Angiotensin II / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Benzimidazoles / pharmacology
  • Blood Pressure / drug effects*
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / physiopathology
  • Dose-Response Relationship, Drug
  • Glomerular Filtration Rate / drug effects
  • Kidney / blood supply
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Male
  • Rats
  • Receptor, Adenosine A1 / metabolism*
  • Renal Circulation / drug effects
  • Tetrazoles / pharmacology
  • Vascular Resistance / drug effects
  • Xanthines / pharmacology

Substances

  • Adenosine A1 Receptor Antagonists
  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Receptor, Adenosine A1
  • Tetrazoles
  • Xanthines
  • Angiotensin II
  • 1,3-dipropyl-8-cyclopentylxanthine
  • candesartan