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Inhibition of tubuloglomerular feedback during adenosine1 receptor blockade
J Schnermann1, H Weihprecht, J P Briggs
1Department of Physiology, University of Michigan, Ann Arbor 48109.
Abstract:
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.
Insights
The adenosine1 (A1) receptor antagonist CPX significantly reduced tubuloglomerular feedback (TGF) responses in rats. This indicates A1-receptor activation on afferent arterioles mediates TGF.
Area of Science:
- Nephrology
- Pharmacology
- Physiology
Background:
- Tubuloglomerular feedback (TGF) is a key intrarenal mechanism regulating glomerular filtration rate.
- Adenosine acting via A1 receptors is implicated in TGF, but its precise role needs further elucidation.
Purpose of the Study:
- To investigate the role of adenosine1 (A1) receptors in mediating tubuloglomerular feedback (TGF) responses.
- To determine the effect of the selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on TGF.
Main Methods:
- Experiments were conducted in anesthetized rats.
- TGF responses were assessed by measuring the maximum change in stop-flow pressure (PSF).
- The A1 receptor antagonist CPX was administered luminally, peritubularly, and into neighboring nephrons.
Main Results:
- Luminal, peritubular, and intra-nephron administration of CPX significantly reduced TGF-mediated PSF responses.
- The A1 receptor agonist N6-cyclohexyladenosine (CHA) reduced PSF, an effect blunted by CPX.
- CPX selectively inhibited the effects of CHA, confirming its A1 receptor antagonism.
Conclusions:
- Activation of A1 receptors on vascular cells of the afferent arterioles plays a crucial role in mediating TGF responses.
- Selective A1 receptor antagonism effectively attenuates TGF, highlighting the therapeutic potential of targeting this pathway.