Effect of adenosine analogues on tubuloglomerular feedback responses.
Adenosine has been invoked as a possible mediator of the vasoconstrictor response elicited through the tubuloglomerular feedback mechanism. These experiments were undertaken to study the effect of adenosine analogues on the magnitude of the stop-flow pressure (SFP) feedback response. With a control solution, maximum change of SFP during orthograde perfusion was 6.3 +/- 0.34 mmHg. When the adenosine1 (A1) receptor agonists CHA, CPA, or R-PIA were present in the perfusate in a concentration of 10(-5) M, SFP responses were significantly augmented and averaged 12.6 +/- 1.9 (P less than 0.001), 12.6 +/- 0.8 (P less than 0.001), and 10.3 +/- 1.1 mmHg (P less than 0.02), respectively. Diminished responses were seen at higher concentrations of A1 analogues. The A2-receptor agonist NECA did not significantly modify the control response at 10(-5) M, but reduced its magnitude at higher concentrations. During graded increases in loop flow rate essentially all of the response in the presence of CPA or R-PIA occurred in the 0-10 nl/min flow interval, whereas the most sensitive flow rate range in the control tubules was between 10 and 20 nl/min. In the presence of 10(-4) M furosemide SFP responses were abolished during perfusion with the control and NECA-containing solutions. In contrast, SFP fell by 11.8 +/- 1.26 mmHg and 8.7 +/- 1.25 mmHg with CHA or CPA solutions despite the presence of furosemide. Perfusion with 10(-6) M CPA in an isotonic mannitol solution was associated with a decrease of SFP by 16.3 +/- 1.42 mmHg, whereas the mannitol solution alone decreased SFP by only 0.6 +/- 0.18 mmHg. Our results show that luminal administration of A1-receptor analogues increases SFP feedback response magnitude, an effect that does not require the presence of a luminal NaCl signal.
Schnermann
J
J
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D006706:Homeostasis; D007606:Juxtaglomerular Apparatus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000378:metabolism
D011983:Receptors, Purinergic; C047235:N-(1-methyl-2-phenylethyl)adenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine