MODULATION OF TUBULOGLOMERULAR FEEDBACK RESPONSIVENESS BY EXTRACELLULAR ATP

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 maxi-mal 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). In contrast, the magnitude of the mean SFP feedback response to a late proximal perfusion rate of 40 nl/min was only slightly reduced during peritubular capillary infusion of 10(-3) M adenosine (11.7 +/- 1.3 vs. 9.6 +/- 1.2 mmHg; P < 0.05, n = 12). The present findings indicate that ATP can increase preglomerular vascular resistance during conditions of adenosine receptor blockade and suggest a role for extracellular ATP, acting via specific P2 purinoceptors, in the regulation of tubuloglomerular feedback responsiveness.