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 and released with norepinephrine (NE) from central and peripheral adrenergic neurons and has been suggested to contribute to the control of vascular tone. This study was undertaken to assess the contribution of NPY at the vascular adrenergic neuroeffector junction in the rat kidney. Experiments were performed in isolated rat kidneys prelabeled with tritiated NE ([3H] NE). Infusion of NPY (1-50 nM) resulted in a dose-dependent increase in basal perfusion pressure and potentiated the vasoconstrictor response elicited by renal nerve stimulation (RNS; 0.5-4 Hz). NPY (10-50 nM) also potentiated the vasoconstrictor response elicited 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 increase 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 efflux. Periarterial nerve stimulation at 4 and 10 Hz resulted in release of immunoreactive NPY by 8- and 38-fold, respectively. These data indicate that NPY acts primarily at the postjunctional sites to produce renal vasoconstriction and to potentiate the vasoconstrictor response to RNS via Y1 receptors. Furthermore, NPY coreleased with adrenergic transmitter may also inhibit release of NE at higher frequencies of RNS (8-16 Hz) by acting on Y1 receptors at the prejunctional sites.
Department of Pharmacology, University of Tennessee, Memphis.
W F
WF
Oellerich
K U
KU
Malik
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation*; D008297:Male; D008969:Molecular Sequence Data; D009451:Neuroeffector Junction / Q000187:drug effects* / Q000502:physiology*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D012077:Renal Artery / Q000187:drug effects / Q000294:innervation; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C062924:neuropeptide Y (13-36); D014316:Tritium; C062259:neuropeptide Y, Leu(31)-Pro(34)-; C083228:PYX 1; C079216:PYX 2; D009638:Norepinephrine