Involvement of sympathetic efferents but not capsaicin-sensitive afferents in nociceptin-mediated dual control of rat synovial blood flow.
This study set out to examine the vasomotor effects of the opioid-like peptide nociceptin on knee joint capsular blood flow in urethane-anaesthetized rats. Topical application of nociceptin (10(-15)-10(-8) mol) caused a progressive fall in joint perfusion that was significantly inhibited by the specific nociceptin receptor antagonist [Phe(1)-(CH(2)-NH)-Gly(2)] Nociceptin(1-13)-NH(2) as well as the nonspecific opioid antagonist naloxone. To test whether this constrictor response was sympathetically mediated, we administered nociceptin in animals treated with guanethidine to produce sympathetic blockade or in the presence of the alpha-adrenoceptor antagonist phentolamine. Both guanethidine treatment and phentolamine coadministration attenuated the constrictor response to nociceptin. Inhibition of nociceptin-mediated vasoconstriction revealed a supplementary hyperemic response that persisted in animals whose knee joints were treated with 1% capsaicin to destroy the articular unmyelinated nerve supply. These results show that, in the rat knee, peripheral administration of nociceptin primarily causes a sympathetically mediated vasoconstriction. In addition, high-dose nociceptin produces a vasodilatatory response that is likely due to the direct action of nociceptin on vascular smooth muscle and not by a neurogenic mechanism.
McDougall
Jason J
JJ
Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada T2N 4N1. mcdougaj@ucalgary.ca
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000344:Afferent Pathways / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000502:physiology*; D004558:Electric Stimulation; D006145:Guanethidine / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply / Q000502:physiology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013583:Synovial Membrane / Q000098:blood supply* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D000097629:Nociceptin
D002211:Capsaicin; D006145:Guanethidine; D009270:Naloxone; D018847:Opioid Peptides; D000097629:Nociceptin