NERVE-MEDIATED RESPONSES OF BLOOD-VESSELS IN THE RABBIT KNEE-JOINT

Blood vessels in the anterior region of the knee joint of anaesthetise d rabbits showed a biphasic response to the electrical stimulation (10 Hz, 1 ms width, 10 V amplitude) of nerve fibres supplying the knee, a s measured by laser Doppler flowmetry. The response consisted of vasoc onstriction during nerve stimulation followed by a prolonged dilatatio n. The vasoconstrictor response was mediated by noradrenaline acting m ainly via alpha1-adrenoceptors as it was substantially reduced by clos e intra-arterial injection of the alpha-adrenergic antagonist phentola mine (approximately 50% reduction) and the selective alpha1-adrenergic antagonist prazosin (approximately 50% reduction) but not by the alph a2-antagonist rauwolscine. Further studies involving prolonged (2-hour ) close intra-arterial infusion of prazosin gave a approximately 50% r eduction of the constrictor response with a concentration of 10(-5) M and approximately 95% reduction when the concentration was raised to 1 0(-4) M. At the higher prazosin concentration responses to close intra -arterial injection of the alpha1-agonist phenylephrine were substanti ally reduced but responses to the alpha2-agonists clonidine and UK-143 04 were not significantly influenced. Infusions of the alpha2 antagoni st CH 38083 failed to inhibit nerve-mediated vasoconstriction at 10(-5 ) or 10(-4) M. There did not appear to be a purinergic component, as t he constrictor response was unaffected by the P2x desensitiser alpha,b eta-methylene adenosine 5'-triphosphate. The dilator response appeared to be mediated principally by substance P (presumably released from s ensory C fibers) as it was substantially reduced by intraarticular inj ection of substance P antagonist D-Pro4D-Trp7,9,10-SP(4-11). These res ults indicate that in the anterior region of the rabbit knee joint alp ha1-adrenoceptors mediate vasoconstriction during electrical stimulati on of the nerve supply to joint blood vessels and suggest that the neu rotransmitter is likely to be noradrenaline. The dilator response may arise from activation of sensory (C) nerve fibres containing substance P which could have a pathophysiological role in inflammatory joint di sease.