We have previously shown that Peptide YY (PYY) causes vasoconstriction in the rat kidney, without affecting sodium excretion. Because PYY is a ligand for the NPY receptor in the kidney, and NPY is present in renal adrenergic nerves, we investigated the effect of renal denervation (DNV) on the density of receptors and the subsequent effect of PYY on renal blood flow (RBF). The left kidneys of Sprague-Dawley rats were surgically DNV by stripping the vascular pedicle of adventitia and painting with 10% phenol. Binding and RBF studies were done 1 week post-DNV. DNV was confirmed by measuring renal norepinephrine content (<4% of control). Binding studies with 125I-PYY on kidney slices showed a greater density of receptors in DNV than control. RBF was measured by electromagnetic flowmeter. Bolus injections of PYY (10, 5, 2.5. 1. or 0.5 pmols) or angiotensin II (4, 2, 1, 0.5, or 0.25 pmolsl were given in random order via a renal artery catheter. DNV had no significant effect on vasoconstriction by All. PYY caused a significantly greater vasoconstriction in DNV than in control at 10. 5, and 2.5 pmols (control RBF deer, by 17.5±3% ,15.5±1.6%, and 10.1±1.1%. and DNV deer, by 30.6±2.8%. 20.6±2.3%, and 14.9±2.2%: P<0.05). These results indicate that DNV is associated with upregulation of NPY receptors in renal parenchyma, and augmented vasoconstrictive response to PYY. (NC Heart Grant NC95GS20).