Nerve-mediated responses of blood vessels in the rabbit knee joint

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 alpha 1-adrenoceptors as it was substantially reduced by close intra-arterial injection of the alpha-adrenergic antagonist phentolamine (approximately 50% reduction) and the selective alpha 1-adrenergic antagonist prazosin (approximately 50% reduction) but not by the alpha 2-antagonist rauwolscine. Further studies involving prolonged (2-hour) close intra-arterial infusion of prazosin gave a approximately 50% reduction of the constrictor response with a concentration of 10(-5) M and approximately 95% reduction when the concentration was raised to 10(-4) M. At the higher prazosin concentration responses to close intra-arterial injection of the alpha 1-agonist phenylephrine were substantially reduced but responses to the alpha 2-agonists clonidine and UK-14304 were not significantly influenced. Infusions of the alpha 2 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 P2X desensitiser alpha,beta-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 intraarticular injection of substance P antagonist D-Pro4D-Trp7,9,10-SP(4-11).(ABSTRACT TRUNCATED AT 250 WORDS)