Sympathetic regulation of skeletal muscle blood flow in the pig: a non-adrenergic component likely to be mediated by neuropeptide Y.

The sympathetic regulation of blood flow in the skeletal muscle of the pig hind limb was investigated. Electrical stimulation of the lumbar sympathetic nerve with single impulses under control conditions decreased hind limb vascular conductance by 32%. After reserpine treatment combined with interruption of the sympathetic nerve activity in order to deplete the noradrenaline (NA) content, about 25% of the vasoconstrictor responses to single impulse stimulation still remained. In addition, an atropine sensitive dilatory component in the vascular response was also observed after reserpine treatment. Furthermore, intermittent stimulation with 20 Hz bursts (for 2 min) after reserpine caused a large vasoconstriction which was about 80% of the control response and lasted twice as long (about 15 min). This response was not affected by administration of the alpha-adrenoceptor antagonist phenoxybenzamine or the stable ATP-analogue alpha, beta-methylene-ATP. Furthermore, in the reserpine pretreated pigs 20 Hz burst stimulation caused detectable overflow of neuropeptide Y (NPY)-like immunoreactivity while NA release was reduced by 90%. Intra-arterial administration of the NPY analogues [Leu31Pro34]NPY (Y1-receptor agonist) and NPY(13-36) (Y2-receptor agonist) evoked dose dependent and long-lasting vasoconstriction, whereby the Y1 agonist was about 10-fold more potent than the Y2 agonist. In conclusion, the sympathetic regulation of the pig hind limb vasculature involves adrenergic, cholinergic and non-adrenergic mechanisms. Several indirect lines of evidence suggest that the non-adrenergic constrictor component, which is present even upon single impulse stimulation, is caused by NPY, possibly acting on Y1 receptors.