P2X Receptor Blockade Inhibits Autoregulation of Renal Blood Flow In Vivo

Abstract

P2X1 receptor activation is implicated in afferent arteriolar autoregulatory behavior in vitro. Experiments were performed to test the hypothesis that P2X receptor blockade with pyridoxal phosphate‐6‐azo‐benzene‐2,4‐disulfonic acid (PPADS, 20μmoles/kg) inhibits renal autoregulation in vivo. An occluder, placed around the aorta, was used to adjust renal arterial pressure in 10mmHg decrements. Autoregulatory profiles of renal blood flow (RBF) were measured before and during P2 receptor blockade using an ultrasonic flow probe placed around the left renal artery. Baseline RBF was similar between control and PPADS treated groups, averaging 8.3±0.7 and 8.4±0.6 ml/min, respectively. Under control conditions, the change in RBF averaged 0.7±0.9% (0.0±0.1 ml/min; n=6) at arterial pressures between 100 and 120 mmHg. Conversely, RBF decreased by 10.5±1.4% (0.8±0.2 ml/min; n=5; P<0.05) over the same pressure range, during PPADS treatment. Bolus i.v. infusions of a P2X1 receptor selective agonist, α, β‐methylene ATP (αβ‐mATP), reduced RBF dose‐dependently. 500ng of αβ‐mATP increased mean arterial pressure (MAP) by 8.2±0.7mmHg and reduced RBF by 50% from 6.1±0.4 to 3.0±0.7ml/min. During PPADS treatment, the effects of αβ‐mATP (500ng) on MAP and RBF were eliminated. These data support the hypothesis that P2X1 receptor activation is essential for initiating autoregulation in vivo.