Direct assessment of renal microvascular responses to P2-purinoceptor agonists.

摘要

Studies were performed to determine the responsiveness of rat juxtamedullary afferent arterioles to receptor-selective P2-purinoceptor agonists. Experiments were performed in vitro using the blood perfused juxtamedullary nephron technique, combined with videomicroscopy. Renal perfusion pressure was set at 110 mmHg and held constant. Basal afferent arteriolar diameter averaged 22.0 +/- 0.6 microns (n = 69). Stimulation with 0.1, 1.0, 10, and 100 microM ATP (n = 10) elicited a concentration-dependent vasoconstriction averaging 8 +/- 2, 17 +/- 2, 21 +/- 4, and 23 +/- 5%, respectively. A nearly identical afferent arteriolar vasoconstriction was observed in response to the P2X-selective agonist beta,gamma-methylene ATP (n = 10); however, another P2X agonist, alpha,beta-methylene ATP, evoked marked receptor desensitization (n = 10). Vessel diameter decreased by approximately 7 +/- 2, 16 +/- 2, 23 +/- 3, and 22 +/- 3%, respectively, over the same concentration range. The P2Y-selective agonist, 2-methylthio-ATP, evoked only a modest vasoconstriction, whereas UTP and adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) reduced afferent diameter markedly at concentrations > 1.0 microM. Afferent arteriolar diameter decreased by 5 +/- 4, 31 +/- 8, and 72 +/- 8% during UTP administration (n = 7) at concentrations of 1.0, 10, and 100 microM, respectively. Similarly, ATP gamma S (n = 6) decreased afferent diameter by 16 +/- 2, 58 +/- 8, and 98 +/- 3%, respectively, over the same concentration range. Nitric oxide synthesis inhibition with N omega-nitro-L-arginine did not significantly alter the afferent arteriolar response to ATP but did potentiate ATP-mediated arcuate artery vasoconstriction. The following data suggest the presence of multiple P2 receptors on juxtamedullary afferent arterioles and are consistent with classification of those receptors as members of the P2X- and P2Y2 (P2U)-receptor subtypes.