SYMPATHETIC AND PARASYMPATHETIC INTERACTION IN VASCULAR AND SECRETORYCONTROL OF THE NASAL MUCOSE IN ANESTHETIZED DOGS

1. In dogs anaesthetized with pentobarbitone, electrical stimulation o f the parasympathetic nerve fibres to the nasal mucosa evoked frequenc y dependent increases in both nasal arterial blood flow and nasal secr etion. Blood flow was measured using a transonic flow probe placed aro und the artery. 2. Sympathetic nerve stimulation for 3 min at 10 Hz ev oked significant and prolonged (> 30 min) attenuation of the vasodilat or and secretory responses to subsequent parasympathetic stimulation. 3. Intravenous and intranasal administration of the neuropeptide Y (NP Y) analogue N-acetyl [Leu(28),Leu(31)] NPY 24-36, a selective NPY Y-2 receptor agonist (20 nmol kg(-1)), significantly attenuated both vasod ilator and secretory effects of subsequent parasympathetic nerve stimu lation. When given intravenously the inhibitory effect of this Y-2 rec eptor agonist on vascular and secretory effects of parasympathetic ner ve stimulation was rapid in onset (5 min) and lasted for more than 60 min. The modulatory effect of the Y-2 receptor agonist was also seen w ith intranasal administration, but was slower in onset (15 min), and l asted less than 45 min. The effects of the intranasal pretreatment wit h the Y-2 receptor agonist were significantly prolonged in the presenc e of the endopeptidase inhibitor phosphoramidon (10 nM). 4. Atropine p retreatment did not significantly reduce the change in vascular conduc tance evoked by parasympathetic nerve stimulation. Subsequent pretreat ment with the NPY Y-2 receptor agonist N-acetyl [Leu(28),Leu(31)] NPY 24-36 reduced the stimulation induced increase in conductance by 30%. Nasal secretion was reduced by 70% following pretreatment with atropin e and a further 30% by pretreatment with the NPY Y-2 receptor agonist. Dose dependent vasodilator and secretory effects of local intra-arter ial infusion of acetylcholine and vasoactive intestinal peptide were n ot modified by the NPY Y-2 agonist. 5. Total protein and albumin conce ntration were measured in nasal lavage fluid collected after nerve sti mulation. Atropine pretreatment increased the percentage of tile total protein that was albumin in nasal lavage fluid. Neither sympathetic n erve stimulation nor Y-2 receptor agonist pretreatment further modifie d the albumin exudation (a marker of vascular permeability) in nasal f luid las age collected after parasympathetic nerve stimulation. 6. We propose that sympathetic nerve stimulation releases NPY, which acts on Y-2 receptors, probably located on parasympathetic nerve endings, to attenuate both vasodilatation and nasal secretion evoked by subsequent parasympathetic nerve stimulation. This effect is also observed after pretreatment with the Y-2-selective NPY analogue N-acetyl [Leu(28),Le u(31)] NPY 24-36.