M 1and M 3 muscarinic receptors mediate relaxation and contraction in canine nasal veins

Abstract

Background: Acetylcholine (ACh) has been shown to induce nasal congestion via vasorelaxation of intranasal posterior collecting veins (PCV) coupled with vasocontraction of extranasal outflow veins (dorsal nasal vein [DNV] and sphenopalatine vein [SPV]). The aim of this study was to characterize the muscarinic receptor subtype(s) involved in ACh-induced relaxation and contraction in canine nasal veins. Methods: PCV, DNV, and SPV were isolated from the canine nose. In vitro isometric tension of segments from these veins was monitored to reflect vascular reactivity. ACh concentration-response curve was studied in the presence of muscarinic receptor subtype inhibitors. Immunohistochemical localization of M 1-M 5 receptor subtypes in the veins was performed. Results: ACh-induced relaxation in PVC was inhibited by pertussis toxin (PTX; inhibitor of G-protein that couples M2/M4 receptors), methoctramine (selective M 2 muscarinic receptor inhibitor), muscarinic toxin 7 (MT-7; selective M 1 muscarinic receptor inhibitor), and 4-diphenylacetoxy-methylpiperidine methiodide (4-DAMP; selective M3 muscarinic receptor inhibitor). ACh-induced contraction in SPV and DNV was potentiated by PTX and methoctramine but was inhibited by MT-7 and 4-DAMP. Immunohistochemistry confirmed the presence of five muscarinic receptor subtypes in the endothelium of nasal veins, with staining of M 3 > M 1 > M 5 > M 2 > M 4 in PVC but M 2 > M 4 > M 3 > M 1 > M 5 in outflow veins. M1 and M3 receptor subtypes were localized in the smooth muscles of both types of veins. Conclusion: The results show that ACh relaxes intranasal veins and contracts extranasal veins primarily via M 1 and M 3 muscarinic receptor subtypes, implying the therapeutic value of M 1/M 3-specific or highly selective anticholinergics on nasal congestion. Copyright © 2011, OceanSide Publications, Inc.