Nerve-Mediated Responses of Blood Vessels in the Rabbit Knee Joint

Abstract

Blood vessels in the anterior region of the knee joint of anaesthetised rabbits showed a biphasic response to the electrical stimulation (10 Hz, 1 ms width, 10 V amplitude) of nerve fibres supplying the knee, as measured by laser Doppler flowmetry. The response consisted of vasoconstriction during nerve stimulation followed by a prolonged dilatation. The vasoconstrictor response was mediated by noradrenaline acting mainly via α₁-adrenoceptors as it was substantially reduced by close intra-arterial injection of the α-adrenergic antagonist phentolamine (∼50% reduction) and the selective α₁-adrenergic antagonist prazosin (∼50% reduction) but not by the α₂-antagonist rauwolscine. Further studies involving prolonged (2-hour) close intra-arterial infusion of prazosin gave a ∼ 50% reduction of the constrictor response with a concentration of 10^-5 M and ∼95% reduction when the concentration was raised to 10^-4 M. At the higher prazosin concentration responses to close intra-arterial injection of the α₁-agonist phenylephrine were substantially reduced but responses to the α₂-agonists clonidine and UK-14304 were not significantly influenced. Infusions of the α₂ antagonist 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 the constrictor response was unaffected by the P_2x desensitiser αβ-methylene adenosine 5’-triphosphate. The dilator response appeared to be mediated principally by substance P (presumably released from sensory C fibers) as it was substantially reduced by intra-articular injection of substance P antagonist D-Pro⁴D-Trp^7,9,10-SP(4-ll). These results indicate that in the anterior region of the rabbit knee joint α -adrenoceptors mediate vasoconstriction during electrical stimulation of the nerve supply to joint blood vessels and suggest that the neurotransmitter is likely to be noradrenaline. The dilator response may arise from activation of sensory (C) nerve fibres containing substance P which could have a patho-physiological role in inflammatory joint disease.