Modulation of tubuloglomerular feedback responsiveness by extracellular ATP

Am J Physiol. 1993 Mar;264(3 Pt 2):F458-66. doi: 10.1152/ajprenal.1993.264.3.F458.

Abstract

Experiments were performed in pentobarbital sodium-anesthetized rats to determine the effects of activation of P2 purinoceptors sensitive to ATP on glomerular capillary pressure, as estimated from proximal tubule stop-flow pressure (SFP) measurements, and on the magnitude of maximal tubuloglomerular feedback-mediated reductions in SFP. To selectively expose nephrons in vivo to ATP without influencing arterial blood pressure, we infused ATP directly into the surrounding peritubular capillaries. Peritubular capillary infusion, at a rate of 20 nl/min, of an isotonic saline solution containing 10(-3) M ATP elicited a transient decrease in resting SFP. However, subsequent infusion of 10(-3) M ATP together with the adenosine receptor (P1 purinoceptor) antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (PSPX, 10(-3) M) into the same vascular sites elicited a sustained decrease in resting SFP. Peritubular infusion of the slowly metabolizable ATP analogue, beta,gamma-methylene-ATP (10(-3) M), at a rate of 20 nl/min, also elicited a transient decrease in SFP, but this was not converted to a sustained response by PSPX. The SFP feedback responses to a late proximal perfusion rate of 40 nl/min were markedly attenuated during peritubular infusion of either 10(-3) M ATP (8.7 +/- 1.2 vs. 1.8 +/- 0.9 mmHg; P < 0.01, n = 9) or 10(-3) M beta,gamma-methylene-ATP (8.2 +/- 1.3 vs. 2.2 +/- 1.2 mmHg; P < 0.01, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / administration & dosage
  • Adenosine / pharmacology
  • Adenosine Triphosphate / administration & dosage
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Capillaries / drug effects
  • Feedback
  • Kidney Glomerulus / blood supply*
  • Kidney Glomerulus / drug effects
  • Kidney Tubules / blood supply*
  • Kidney Tubules / drug effects
  • Male
  • Purinergic Antagonists
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Resistance / drug effects
  • Xanthines / pharmacology

Substances

  • Purinergic Antagonists
  • Xanthines
  • 5'-adenylyl (beta,gamma-methylene)diphosphonate
  • 1,3-dipropyl-8-(4-sulfophenyl)xanthine
  • Adenosine Triphosphate
  • Adenosine
  • alpha,beta-methyleneadenosine 5'-triphosphate