Norepinephrine and neuropeptide Y: vasoconstrictor cooperation in vivo and in vitro.
Norepinephrine (NE)-evoked vasoconstrictor and pressor responses are reduced after prolonged exposure; such desensitization is observed both clinically and experimentally. The vasoconstrictor neuropeptide Y (NPY) coexists with NE in perivascular sympathetic nerves, and the results of both in vivo and in vitro studies have indicated functional cooperation between NE and NPY. We propose that NPY becomes increasingly important in situations of high sympathetic activity associated with blunted NE responses. Prolonged NE infusion in conscious rats resulted in adrenergic desensitization; however, NPY administration restored the responsiveness to NE. In naive rats, NE greatly enhanced the pressor action of NPY. An analogous phenomenon was observed in the rabbit isolated pulmonary artery, which failed to respond to NPY unless preexposed to NE; this action of NE was only partly inhibited by conventional adrenoceptor and Ca2+ influx blockade. Conversely, NPY enhanced NE-evoked constriction, in particular when the alpha-adrenoceptor reserve was eliminated. It is proposed that threshold synergism, in part caused by converging stimulation of phospholipase C, accounts for much of the NPY/NE cooperativity. We conclude that 1) NPY and NE cooperate to produce vasoconstriction, both in vivo and in vitro; 2) NPY has the capacity to reverse adrenergic desensitization but not vice versa; 3) NE enhances NPY-evoked vasoconstriction, in part independently of conventional adrenoceptor blockade; 4) threshold synergism phenomena, but not "receptor-receptor interactions," account for (most of) the observed NPY/NE cooperation; and 5) when present, alpha-adrenoceptor reserve prevents the lowering of the NE threshold by NPY.
Wahlestedt
C
C
Department of Neurology, Cornell University Medical College, New York, New York 10021.
Håkanson
R
R
Vaz
C A
CA
Zukowska-Grojec
Z
Z
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003243:Consciousness; D003538:Cystamine / Q000494:pharmacology / Q000031:analogs & derivatives; D004357:Drug Synergism; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007295:Inositol Phosphates; D009478:Neuropeptide Y; D014662:Vasoconstrictor Agents; C029998:benextramine; D003538:Cystamine; D009638:Norepinephrine; D011224:Prazosin