The role of joint nerves and mast cells in the alteration of vasoactive intestinal peptide (VIP) sensitivity during inflammation progression in rats

• Published in: British journal of pharmacology 2005-05, Vol.145 (1), p.104-113
• Main Authors: McDougall, Jason J, Barin, Ali Kursat
• Format: Article
• Language: English
• Subjects: Animals; Arthritis; Arthritis - physiopathology; Biological and medical sciences; blood flow; Hindlimb; Joints - blood supply; Joints - innervation; knee joint nerves; Male; mast cells; Mast Cells - physiology; Medical sciences; neurogenic inflammation; neuropeptides; Pharmacology. Drug treatments; Rats; Rats, Wistar; vasoactive intestinal peptide; Vasoactive Intestinal Peptide - pharmacology; Vasodilator Agents - pharmacology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0706169

1 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. 2 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 × 10−11 mol. The dilator effect of the peptide was transient with the maximal response occurring approximately 1 min after drug administration. 3 VIP‐induced vasodilatation was blocked by co‐administration of the VIP receptor antagonist VIP6–28 (10−9 mol). The inhibitory effect of the antagonist was consistent across the entire VIP dose range (P=0.01). 4 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. 5 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). 6 Stabilisation of synovial mast cells by disodium cromoglycate (cromolyn) pretreatment did not alter the vasoresponsiveness to VIP in acute or chronically inflamed joints. 7 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. British Journal of Pharmacology (2005) 145, 104–113. doi:10.1038/sj.bjp.0706169