Muscarinic blockade of methacholine induced airway and parenchymal lung responses in anaesthetised rats
- Division of Clinical Sciences, TVW Telethon Institute for Child Health Research & University of Western Australia Department of Paediatrics, Perth, Australia and Department of Medical Informatics and Engineering, Albert Szent-Györgyi Medical University, Szeged, Hungary
- Dr M K Tulić, Division of Clinical Sciences, TVW Telethon Institute for Child Health Research, P O Box 855, West Perth, WA 6872, Australia.
- Received 20 July 1998
- Revision requested 3 September 1998
- Revised 24 December 1998
- Accepted 1 February 1999
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 M1receptors 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 (10 or 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.
