P2X1receptor blockade inhibits whole kidney autoregulation of renal blood flow in vivo

Abstract

In vitro experiments demonstrate that P2X1receptor activation is important for normal afferent arteriolar autoregulatory behavior, but direct in vivo evidence for this relationship occurring in the whole kidney is unavailable. Experiments were performed to test the hypothesis that P2X1receptors are important for autoregulation of whole kidney blood flow. Renal blood flow (RBF) was measured in anesthetized male Sprague-Dawley rats before and during P2 receptor blockade with PPADS, P2X1receptor blockade with IP5I, or A1receptor blockade with DPCPX. Both P2X1and A1receptor stimulation with α,β-methylene ATP and CPA, respectively, caused dose-dependent decreases in RBF. Administration of either PPADS or IP5I significantly blocked P2X1receptor stimulation. Likewise, administration of DPCPX significantly blocked A1receptor activation to CPA. Autoregulatory behavior was assessed by measuring RBF responses to reductions in renal perfusion pressure. In vehicle-infused rats, as pressure was decreased from 120 to 100 mmHg, there was no decrease in RBF. However, in either PPADS- or IP5I-infused rats, each decrease in pressure resulted in a significant decrease in RBF, demonstrating loss of autoregulatory ability. In DPCPX-infused rats, reductions in pressure did not cause significant reductions in RBF over the pressure range of 100–120 mmHg, but the autoregulatory curve tended to be steeper than vehicle-infused rats over the range of 80–100 mmHg, suggesting that A1receptors may influence RBF at lower pressures. These findings are consistent with in vitro data from afferent arterioles and support the hypothesis that P2X1receptor activation is important for whole kidney autoregulation in vivo.