DIRECT ASSESSMENT OF RENAL MICROVASCULAR RESPONSES TO P2-PURINOCEPTORAGONISTS

Studies were performed to determine the responsiveness of rat juxtamed ullary afferent arterioles to receptor-selective P2-purinoceptor agoni sts. Experiments were performed in vitro using the blood perfused juxt amedullary nephron technique, combined with videomicroscopy. Renal per fusion pressure was set at 110 mmHg and held constant. Basal afferent arteriolar diameter averaged 22.0 +/- 0.6 mu m (n = 69). Stimulation w ith 0.1, 1.0, 10, and 100 mu M ATP (n = 10) elicited a concentration-d ependent vasoconstriction averaging 8 +/- 2, 17 +/- 2, 21 +/- 4, and 2 3 +/- 5%, respectively. A nearly identical afferent arteriolar vasocon striction was observed in response to the P2X-selective agonist beta,g amma-methylene ATP (n = 10); however, another P2X agonist, alpha,beta- methylene ATP, evoked marked receptor desensitization (n = 10). Vessel diameter decreased by similar to 7 +/- 2, 16 +/- 2, 23 +/- 3, and 22 +/- 3%, respectively, over the same concentration range. The P2Y-selec tive agonist, 2-methylthio-ATP, evoked only a modest vasoconstriction, whereas UTP and adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) red uced afferent diameter markedly at concentrations >1.0 mu M. Afferent arteriolar diameter decreased by 5 +/- 4, 31 +/- 8, and 72 +/- 8% duri ng UTP administration (n = 7) at concentrations of 1.0, 10, and 100 mu M, respectively. Similarly, ATP gamma S (n = 6) decreased afferent di ameter by 16 +/- 2, 58 +/- 8, and 98 +/- 3%, respectively, over the sa me 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 vasocon striction. The following data suggest the presence of multiple P2 rece ptors on juxtamedullary afferent arterioles and are consistent with cl assification of those receptors as members of the P2X- and P2Y(2) (P2U )-receptor subtypes.