Inhibition of tubuloglomerular feedback during adenosine1 receptor blockade.
Experiments were performed in anesthetized rats to study the effect of the selective adenosine1 (A1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on tubuloglomerular feedback (TGF) responses assessed as the maximum change of stop-flow pressure (PSF). Compared with control, PSF responses were reduced during luminal application of CPX at 10(-4) and 10(-5)M (-4.9 +/- 0.44 vs. + 0.9 +/- 0.42 mmHg and -6.8 +/- 0.69 vs. -1.4 +/- 0.7 mmHg, respectively), during peritubular administration of CPX at 10(-4)M (-6.2 +/- 0.44 vs. -2.8 +/- 0.42 mmHg), and during infusion of CPX at 10(-4) M into the lumen of a neighboring nephron (-5.6 +/- 0.6 vs. -1.98 +/- 0.51 mmHg). Selectivity of CPX was tested by studying its effect on the PSF reduction produced by the A1-receptor agonist N6-cyclohexyladenosine (CHA). CHA at 10(-5)M reduced PSF when infused into the peritubular blood (-11.8 +/- 3.7 mmHg), and this effect was blunted by luminal application of CPX (-1.5 +/- 0.6 mmHg). CHA also reduced PSF when infused into a neighboring nephron, and this effect was blunted by infusing CPX at 10(-4)M into the same neighboring nephron, a different neighboring nephron, or a peritubular capillary. These results are consistent with the concept that activation of A1-receptors on vascular cells of the afferent arterioles participates in the mediation of TGF responses.
Schnermann
J
J
Department of Physiology, University of Michigan, Ann Arbor 48109.
Weihprecht
H
H
Briggs
J P
JP
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002196:Capillaries; D005246:Feedback / Q000187:drug effects; D007267:Injections; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000098:blood supply / Q000502:physiology*; D008297:Male; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D014970:Xanthines / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D014970:Xanthines; C027513:N(6)-cyclohexyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine