Influence of P2X receptors on renal medullary circulation is not altered by angiotensin II pretreatment

Abstract

Purine P2X and P2Y receptors (P2-R) are involved in control of renal circulation, especially in the medulla, wherein they appear to interact with angiotensin II (Ang II). Our experimental approach enabled examination of interaction with Ang II per se, in the absence of blood pressure elevation. In this whole-kidney functional study we focused on the influence of P2X1-R on perfusion of the renal medulla. Acute experiments were conducted with normal rats, untreated or subjected to two weeks' infusion of Ang II (osmotic minipumps). Urethane was used for anesthesia because in Ang II-treated rats it normalized elevated blood pressure. MRS2159, a P2X1-R inhibitor, was infused intravenously or directly into the medulla. Renal blood flow (RBF, Transonic renal artery probe), perfusion of the outer and inner medulla (OM-BF, IM-BF; laser-Doppler fluxes), and sodium and water excretion and urine osmolality (Uosm) were measured. In untreated rats intravenous MRS2159 unexpectedly decreased RBF by 12±4% (p<0.02) and IM-BF by 7±2% (p<0.05). In Ang II-pretreated rats the inhibitor tended to increase RBF while OM-BF and IM-BF increased 14±5% and 12±2%, respectively (p<0.05 for both). Renal excretion was not affected, with or without Ang II treatment, while Uosm increased by about 150mosmol/kg H2O (p<0.05). Intramedullary MRS2159 increased IM-BF only, by 21±5% in untreated and 16±3% in Ang II-treated rats (p<0.04 for both). Tonic activity of P2X1 receptors participates in control of renal medullary perfusion and of the tubular processes involved in urine concentration, neither effect is modified by Ang II pretreatment.