M 1 and 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 M₁–M₅ 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 M₂ muscarinic receptor inhibitor), muscarinic toxin 7 (MT-7; selective M₁ 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 M₃ > M₁ > M₅ > M₂ = M₄ in PVC but M₂ = M₄ > M₃ > M₁ > M₅ 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 M₁ and M₃ muscarinic receptor subtypes, implying the therapeutic value of M₁/M₃-specific or highly selective anticholinergics on nasal congestion.