NEUROPEPTIDE-Y MODULATES THE VASCULAR-RESPONSE TO PERIARTERIAL NERVE-STIMULATION PRIMARILY BY A POSTJUNCTIONAL ACTION IN THE ISOLATED-PERFUSED RAT-KIDNEY

Neuropeptide Y (NPY) is a 36-amino acid peptide that is colocalized an d released with norepinephrine (NE) from central and peripheral adrene rgic neurons and has been suggested to contribute to the control of va scular tone. This study was undertaken to assess the contribution of N PY at the vascular adrenergic neuroeffector junction in the rat kidney . Experiments were performed in isolated rat kidneys prelabeled with t ritiated NE ([H-3] NE). Infusion of NPY (1-50 nM) resulted in a dose-d ependent increase in basal perfusion pressure and potentiated the vaso constrictor response elicited by renal nerve stimulation (RNS; 0.5-4 H z). NPY (10-50 nM) also potentiated the vasoconstrictor response elici ted by exogenous NE (150 pmol). These effects of NPY were mimicked by [Leu31,Pro34]NPY, a NPY Y1 receptor agonist whereas [13-36]NPY, a NPY Y2 receptor agonist failed to alter the basal, RNS- or NE-induced incr ease in perfusion pressure. NPY (10 nM) and [Leu31,Pro34 ]NPY but not [13-36] NPY inhibited RNS-induced fractional tritium overflow only at high frequencies of stimulation (10 and 16 Hz) without altering basal tritium eff lux. Periarterial nerve stimulation at 4 and 10 Hz resulte d in release of immunoreactive NPY by 8- and 38-fold, respectively. Th ese data indicate that NPY acts primarily at the postjunctional sites to produce renal vasoconstriction and to potentiate the vasoconstricto r response to RNS via Y1 receptors. Furthermore, NPY coreleased with a drenergic transmitter may also inhibit release of NE at higher frequen cies of RNS (8-16 Hz) by acting on Y1 receptors at the prejunctional s ites.