Acetylcholine induces contractile and relaxant effects in canine nasal venous systems

Abstract

Acetylcholine (ACh) induces nasal congestion at low doses but decongestion at high doses. The current study investigated the vascular mechanisms underlying this biphasic nasal airway response in dogs.Collecting and outflow veins from anterior and posterior nasal venous systems and the septal mucosa (containing sinusoidal venous plexuses) were isolated. The in vitro isometric tension of the vascular segments was monitored to reflect vascular reactivity. Immunohistochemical localisation of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and endothelial nitric oxide synthase (eNOS) was performed.ACh did not affect the venous plexuses but contracted the anterior collecting vein and the outflow veins of both systems in a concentration-dependent manner; the responses were unaffected by nitro-L-arginine-methyl-ester (L-NAME). ACh relaxed posterior collecting veins at low concentrations but contracted them at higher concentrations; L-NAME enhanced the contractions but inhibited the relaxations, with the inhibition reversed by L-arginine. NADPHdiaphorase and eNOS were located predominantly in the posterior collecting veins.The fact that acetylcholine at low concentrations relaxes posterior collecting veins but contracts other collecting and outflow veins implies that the agonist in vivo may induce nasal congestion by increasing posterior blood volume. At higher concentrations, acetylcholine contracts posterior collecting veins as well, implying diminished blood volume in both venous systems, and consequently nasal decongestion. The induced contraction in posterior collecting veins is nitric oxide-independent, while the induced relaxation is nitric oxide-dependent.

M1 and M3 Muscarinic Receptors Mediate Relaxation and Contraction in Canine Nasal Veins

“…In vitro findings show that ACh at low concentrations relaxes posterior collecting veins (PCV) but constricts other veins while, at higher concentrations, ACh constricts all veins. 7 The results support the hypothesis that the nasal congestion that underlies nasal obstruction is caused by dilatation of intranasal PCVs coupled with constriction of extranasal outflow veins. It is now known that ACh can elicit vasodilatation or vasoconstriction via activation of different muscarinic receptor subtypes.…”

“…The ACh-induced vasodilatation in the nose is nitric oxide dependent, whereas the induced contraction is nitric oxide independent. 7 Results of immunohistochemical studies showed the presence of all five known muscarinic receptor subtypes in the nasal veins, with predominance of M 1 and M 3 in the endothelium of collecting veins and in the smooth muscles of outflow veins. This is in agreement with the findings from the functional experiments in which both M 1 and M 3 are involved in mediating the ACh-induced relaxation in collecting veins or contraction in the outflow veins.…”

“…The cumulative ACh concentration-response curve was established with the tissue held at resting tension or at raised tone; phenylephrine (PE), at concentrations ranging from 1 ϫ 10 Ϫ7 M to 1 ϫ 10 Ϫ5 M, was used to raise the tension to ϳ70% TAT. 7 The five muscarinic receptor subtypes are referred to as M 1 -M 5 . Muscarinic receptors transduce their signals by coupling with G-proteins.…”

“…Dorsal nasal veins (DNV), sphenopalatine veins (SPVs), and PCVs were isolated from the nasal cavity and suspended in tissue baths for measurement of isometric tension. 7 After a 30-min equilibration period, each tissue segment was stretched to its optimal resting tension. The tissue was allowed to equilibrate for another 60 minutes and was washed every 20 minutes during the equilibration period.…”

Role of α2-adrenoceptors in Electrical Field Stimulation–induced Contraction of Pig Nasal Mucosa and Pharmacologic Characterization of a Novel α2C-adrenoceptor Agonist

“…Acetylcholine acts on peripheral muscarinic receptors present on epithelium, submucosal glands, arterial, and capacitance vessels 30 and exerted different actions on components of the nasal vascular bed. 31,32 However, the principal function of the parasympathetic cholinergic nerves is to control nasal mucus secretion 2,33 and not vascular reactivity.…”