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. 1999 Jun;54(6):531–537. doi: 10.1136/thx.54.6.531

Muscarinic blockade of methacholine induced airway and parenchymal lung responses in anaesthetised rats

J Wale 1, F Petak 1, P Sly 1
PMCID: PMC1745489  PMID: 10335008

Abstract

BACKGROUND—It has previously been shown that M1 cholinergic receptors are involved in the parenchymal response to inhaled methacholine in puppies using the M1 selective antagonist pirenzepine. Although M3 receptors are responsible for acetylcholine induced bronchoconstriction in isolated rat lung, the role of M1 receptors has not been determined in the rat in vivo.
METHODS—Anaesthetised, paralysed, open chested Brown Norway rats were mechanically ventilated and the femoral vein cannulated for intravenous injection of drugs. Low frequency forced oscillations were applied to measure lung input impedance (ZL) and computerised modelling enabled separation of ZL into airway and parenchymal components. Atropine (500 µg/kg iv) and pirenzepine (50, 100 or 200 µg/kg iv) were administered during steady state constriction generated by continuous inhalation (1 mg/ml) or intravenous (10or 15 µg/kg/min) administration of methacholine.
RESULTS—Continuous inhalation of methacholine produced a 185% increase in frequency dependent tissue resistance (G) which was effectively inhibited by atropine 500 µg/kg iv (p<0.01, n = 6). Pirenzepine (50, 100 or 200 µg/kg) had a minimal effect on the parenchymal response to inhaled methacholine. A 258% increase in airway resistance (Raw) was induced by continuous intravenous infusion of methacholine and this response was effectively abolished by pirenzepine (p<0.001, n = 5). Cutting the vagi in the cervical region did not alter baseline airway mechanics. Vagotomy did not affect lung responses to intravenous methacholine nor the ability of pirenzepine to reduce these responses.
CONCLUSIONS—In the rat, M1-subtype receptors are functional in airways but not in the tissue.



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Selected References

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