TACHYKININ REGULATION OF BASAL SYNOVIAL BLOOD-FLOW

1 Experiments were performed to investigate the role of endogenously r eleased tachykinins in the regulation of blood flow to the rat knee jo int. Synovial perfusion was assessed by laser Doppler perfusion imagin g, which permitted spatial measurement of relative changes in perfusio n from control (pre drug administration), expressed as the percentage change. Most experiments were performed on the exposed medial aspect o f the knee joint capsule. 2 Neither the selective tachykinin NK1 recep tor antagonist, FK888, nor the selective tachykinin NK2 receptor antag onist, SR48968, significantly influenced synovial blood flow at doses of 10(-12), 10(-10) and 10(-8) mol. However, topical co-administration of these agents produced significant dose-dependent reductions in bas al synovial perfusion of 6.3 +/- 4.6, 12.0 +/- 3.4 and 19.9 +/- 2.6%, respectively; n = 29. The non-selective tachykinin NK1/NK2 receptor an tagonist, FK224, also produced significant (at 10(-10) and 10(-8) mol) , but less potent. reductions in perfusion of 5.3 +/- 4.0, 8.4 +/- 2.2 and 5.9 +/- 2.8%, respectively; n = 25. 3 Topical administration of t he alpha(1)-, alpha(2)-adrenoceptor antagonist phenoxybenzamine elicit ed 31.3 +/- 6.2% increase in blood flow which was substantially reduce d to 10.4 +/- 3.8% by co-administration of the FK888 and SR48968 (both at 10(-8) mol; n = 8-13), suggesting that normally there is sympathet ic vasoconstrictor 'tone' which is opposed by the vasodilator action o f endogenous tachykinins. 4 One week after surgical interruption of th e nerve supply to the knee joint, co-administration of FK888 and SR489 68 (both at 10(-8) mol) now produced slight vasodilatation (6.7 +/- 4. 6%; n = 9) which did not differ significantly from vehicle treatment. Depletion of tachykinins from sensory nerve fibres by systemic capsaic in administration also resulted in abolition of the vasoconstrictor ef fect of FK888 and SR48968 (both at 10(-8) mol), with these agents only producing a slight vasodilatation (2.5 +/- 5.3%; n = 6). 5 By use of a near infra-red laser source it was possible to image knee joint perf usion transcutaneously, the overlying skin being left intact. In this more physiological situation, close intra-arterial injection of the co mbination of FK888 and SR48968 (both at 10(-8) mol) again elicited vas oconstriction (48.8 +/- 16.2% reduction in blood flow; n = 4). 6 These results indicate that endogenous tachykinins may be continuously rele ased from sensory fibres innervating the joint. Basal release of tachy kinins could therefore be an important physiological influence opposin g sympathetic vasoconstrictor tone.