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 M(2)/M(4) 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 M(3) 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. M(1) and M(3) 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.