The mechanism and site of action of clonidine in the rat

The inactin anaesthetized rat shews cardiovascular reflex responses. Heat rate is under sympathetic but not vagal control.Clonidine reduces the heart rate and blood pressure in the inactin anaesthetized rat. The reduction in heart rate involves reducing sympathetic cradiac drive. The fall in blood pressure includes a reduction in peripheral resistance.Using a newly developed "delayed" hindlimb perfusion the reduction in peripheral resistance was seen to be neurally mediated. A peripheral vasodilator action was not seen with clonidine.Clonidine was administered by four different routes which were expected to provide access to selected areas in the brain. Intravenous, intracarotid artery, intraventricular and intravertebral artery. Administration into the ventricular system of the brain was slighty more potent in reducing arterial pressure than intravenous injection. Intracarotid and intravenous were equipotent. Intravertbral was by far the most effective, requiring 5% of the intravenous dose to cause an equivalent cardiovascular response.Autoradiography with H-clonidine was used to locate the injected clonidine. The new CEA Verken tritium sensitive film was used and proved able to detect very low levels of tritium. Each route of administration resulted in a different pattern of distribution.Clonidine administered intravenously distributed evenly throughout the CN3.Intacarotid administration selectively reached rostral areas. Intraventricular administration had the spread limited to periventicular areas.Intravertebral clonidine reached the medulla, pons, areas of the cerebellum and upper areas of the spinal cord.Comparison with the different hypotensive affects led to the conclusion that the site of action was within the medulla but not in the periventricular areas