Abstract
Adenosine A(2) receptors have been suggested to modulate tubuloglomerular feedback (TGF) responses by counteracting adenosine A(1) receptor-mediated vasoconstriction, but the mechanisms are unclear. We tested the hypothesis that A(2A) receptor activation blunts TGF by release of nitric oxide in the juxtaglomerular apparatus (JGA). Maximal TGF responses were measured in male Sprague-Dawley rats as changes in proximal stop-flow pressure (ΔP(SF)) in response to increased perfusion of the loop of Henle (0 to 40 nl/min) with artificial tubular fluid (ATF). The maximal TGF response was studied after 5 min intratubular perfusion (10 nl/min) with ATF or ATF + A(2A) receptor agonist (CGS-21680; 10(-7) mol/l). The interaction with nitric oxide synthase (NOS) isoforms was tested by perfusion with a nonselective NOS inhibitor [N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME); 10(-3) mol/l] or a selective neuronal NOS (nNOS) inhibitor [N(ω)-propyl-L-arginine (L-NPA); 10(-6) mol/l] alone, and with the A(2A) agonist. Blood pressure, urine flow, and P(SF) at 0 nl/min were similar among the groups. The maximal TGF response (ΔP(SF)) with ATF alone (12.3 ± 0.6 mmHg) was attenuated by selective A(2A) stimulation (9.5 ± 0.4 mmHg). L-NAME enhanced maximal TGF responses (18.9 ± 0.4 mmHg) significantly more than L-NPA (15.2 ± 0.7 mmHg). Stimulation of A(2A) receptors did not influence maximal TGF response during nonselective NOS inhibition (19.0 ± 0.4) but attenuated responses during nNOS inhibition (10.3 ± 0.4 mmHg). In conclusion, adenosine A(2A) receptor activation attenuated TGF responses by stimulation of endothelial NOS (eNOS), presumably in the afferent arteriole. Moreover, NO derived from both eNOS and nNOS in the JGA may blunt TGF responses.