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

Meri Tulic, J.L. Wale, F. Petak, Peter Sly

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16 Citations (Scopus)

Abstract

Background-It has previously been shown that M-1, cholinergic receptors are involved in the parenchymal response to inhaled methacholine in puppies using the M-1, selective antagonist pirenzepine. Although M-3, receptors are responsible for acetylcholine induced bronchoconstriction in isolated rat lung, the role of M-1, 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 mu g/kg iv) and pirenzepine (50, 100 or 200 mu g/kg iv) were administered during steady state constriction generated by continuous inhalation (1 mg/ml) or intravenous (10 or 15 mu g/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 mu g/kg iv (p
Original languageEnglish
Pages (from-to)531-537
JournalThorax
Volume54
Publication statusPublished - 1999

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