title: The role of joint nerves and mast cells in the alteration of vasoactive intestinal peptide (VIP) sensitivity during inflammation progression in rats.
abstract: The present study examined the peripheral effects of vasoactive intestinal peptide (VIP) on rat knee joint blood flow during acute and chronic inflammation. The involvement of joint nerves and synovial mast cells on these effects was also investigated. Prior to blood flow assessment, animals were deeply anaesthetised with ethyl carbamate (urethane; 2 mg kg(-1) i.p.). Local application of VIP (10(-13)-10(-9) mol) onto the capsular surface of normal rat knee joints caused a dose-dependent increase in synovial perfusion with an ED50 of 1.2 x 10(-11) mol. The dilator effect of the peptide was transient with the maximal response occurring approximately 1 min after drug administration. VIP-induced vasodilatation was blocked by co-administration of the VIP receptor antagonist VIP(6-28) (10(-9) mol). The inhibitory effect of the antagonist was consistent across the entire VIP dose range (P=0.01). The vasoresponsiveness to VIP was significantly attenuated in acutely inflamed joints; however, surgical denervation of acutely inflamed knees re-established the vasodilator effect of the neuropeptide. Topical application of VIP to 1- and 3-week adjuvant monoarthritic knees produced a hyperaemic response, which was not significantly different from normal (P=0.06 and 0.73 for 1- and 3-week adjuvant treated joints, respectively). Stabilisation of synovial mast cells by disodium cromoglycate (cromolyn) pretreatment did not alter the vasoresponsiveness to VIP in acute or chronically inflamed joints. The vasodilatatory effect of VIP is lost during acute knee joint inflammation and this abrogated effect is neurally dependent. In the chronic phase of knee joint inflammation, VIP-mediated hyperaemia recovers to normal levels. Synovial mast cells do not influence the vasomotor effects of exogenously applied VIP in inflamed knee joints.
authors.affiliation: Department of Physiology and Biophysics, University of Calgary, 3330, Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. mcdougaj@ucalgary.ca
authors.forename: Jason J
authors.initials: JJ
authors.lastname: McDougall
authors.forename: Ali Kursat
authors.initials: AK
authors.lastname: Barin
mesh_terms: D000818:Animals; D001168:Arthritis / Q000503:physiopathology*; D006614:Hindlimb; D007596:Joints / Q000098:blood supply / Q000294:innervation*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D014660:Vasoactive Intestinal Peptide
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