Cardiovascular responses to injections of cholinomimetic drugs into the cerebral ventricles of unanaesthetized dogs.

1. The cardiovascular and behavioural effects of cholinomimetic drugs injected through a cannula chronically implanted into a lateral cerebral ventricle were examined in unanaesthetized dogs.2. Acetylcholine (ACh) (10-20 mug) produced an increase in arterial pressure and heart rate, the dogs became more alert, moved their heads, licked and swallowed and then became drowsy.3. The responses to ACh were potentiated by intraventricular physostigmine (5 mug), were abolished by intraventricular atropine (100 mug) but were unaffected by intraventricular mecamylamine (250 mug). The responses to ACh were reproducible on any one day if injections were given again after a 30 min interval but tolerance developed when ACh was injected repeatedly over periods of several days.4. Methacholine (40 mug) produced similar behavioural and cardiovascular effects to ACh but of a longer duration. The responses to methacholine were abolished by intraventricular atropine (100 mug).5. Nicotine (20-60 mug) produced a biphasic cardiovascular response of an initial brief pressor response and tachycardia followed by a secondary increase in arterial pressure and heart rate which was greater in magnitude and duration. The secondary cardiovascular effects were associated with restlessness and vomiting.6. The responses to nicotine were abolished by prior injection of mecamylamine (250 mug) but were unaffected by atropine (100 mug). The responses to nicotine were not reproducible if injections were repeated on the same day but could be again produced if a few days were allowed to elapse between injections.7. An increased heart rate occurred during the pressor response to the cholinomimetic drugs but when a comparable pressor response was produced by intravenous infusion of noradrenaline in the same unanaesthetized dogs pronounced reflex bradycardia resulted.8. The results indicate that the activation of both muscarinic and nicotinic cholinergic mechanisms leads to cardiovascular and behavioural effects in the conscious dog although the site of action and peripheral mechanisms have not been determined.