Ketamine is a potent bronchodilator, but its mode of action is unclear. We have studied the effect of ketamine on the peripheral vagus nerve motor pathway of isolated porcine trachealis muscle. Postsynaptic nicotinic cholinergic receptors of the intramural ganglia were stimulated selectively with 1,1-dimethyl-4-phenyl-piperazinium iodide, post-ganglionic nerve fibres with electrical field stimulation (in the presence of hexamethonium) and muscarinic cholinergic receptors with acetylcholine (in the presence of tetrodotoxin). Ketamine 10(-4) mol litre-1 significantly shifted the concentration-response curves of acetylcholine (P < 0.02) and electrical field stimulation (P < 0.001) to the right and abolished the response to 1,1-dimethyl-4-phenyl-piperazinium iodide (P < 0.02). Ketamine also caused a concentration-dependent relaxation of muscle strips precontracted with acetylcholine. This was unaffected by propranolol. Ketamine relaxed muscle strips precontracted with potassium chloride, in the absence and presence of atropine. We conclude that ketamine interacts with the peripheral vagus nerve by decreasing the excitability of the postsynaptic nicotinic receptors of the intramural ganglia, and by affecting the muscarinic receptor, smooth muscle, or both. Beta-2 adrenoceptors are not involved in the mechanism of relaxation.

SUMMARYMean arterial pressure (MAP) and heart rate (HR) were measured during static contraction or passive stretch of the triceps surae muscle of chloralose-anaesthetized cats. MAP and HR increased by 46 + 5 mmHg and 17 + 3 beats min-', respectively, during a 1 min contraction.Passive stretch of the same muscle for 1 min reflexly increased MAP and HR by 40 + 7 mmHg and 14 + 3 beats minm , respectively. Microdialysis of 2 mm 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, into the dorsal horn at the L7 spinal level attenuated the reflex pressor response to static contraction (2 h of dialysis: AMAP = 23 + 5 mmHg, AHR = 8 + 2 beats min-'). By contrast, there was no attenuation of the pressor response to passive stretch at 2 h of CNQX perfusion. However, the simultaneous microdialysis of 2 mM CNQX into the L6 and S 1 levels blunted the pressor and tachycardic responses to contraction and stretch. These data show that the reflex pressor response to static muscle contraction is partly mediated by activation of non-NMDA receptors at the level of afferent fibre entry into the dorsal horn and through collateral pathways. Further, it appears that the afferent pathways within the dorsal horn for the signal transduction arising from static muscle contraction and passive stretch of the hindlimb are dissimilar.

The release of substance P and somatostatin in the spinal cord plays a role in mediating the cardiovascular changes caused by static contraction, but the release of other neurotransmitters/neuromodulators is also involved. The attenuation produced by these antagonists is mediated, at least in part, by reducing sympathetic outflow.