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

Background-It has previously been shown that M-1, cholinergic receptors are involved in the parenchymal response to inhaled methacholine in puppies us ing the M-1, selective antagonist pirenzepine. Although M-3, receptors are responsible for acetylcholine induced bronchoconstriction in isolated rat l ung, the role of M-1, receptors has not been determined in the rat in vivo. Methods-Anaesthetised, paralysed, open chested Brown Norway rats were mecha nically ventilated and the femoral vein cannulated for intravenous injectio n of drugs. Low frequency forced oscillations were applied to measure lung input impedance (ZL) and computerised modelling enabled separation of ZL in to airway and parenchymal components. Atropine (500 mu g/kg iv) and pirenze pine (50, 100 or 200 mu g/kg iv) were administered during steady state cons triction 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 f requency dependent tissue resistance (G) which was effectively inhibited by atropine 500 mu g/kg iv (p<0.01, n = 6). pirenzepine (50, 100 or 200 mu g/ kg) had a minimal effect on the parenchymal response to inhaled methacholin e. A 258% increase in airway resistance (Raw) was induced by continuous int ravenous infusion of methacholine and this response was effectively abolish ed 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 resp onses to intravenous methacholine nor the ability of pirenzepine to reduce these responses. Conclusions-In the rat, M-1-subtype receptors are functional in airways but not in the tissue.