Investigation of the central and peripheral actions of clonidine and methoxamine using a new in vivo rat preparation.

A cross-circulation technique was developed in rats to distinguish central from peripheral cardiovascular actions of drugs. The right common carotid arteries were ligated, and the left common carotid arteries and left and right external jugular veins of two pentobarbital-anesthetized rats were connected with PE tubing so that peripheral blood from one rat, A, supplied the head of another rat, B, and then returned to the body of A, and vice versa, for peripheral blood from rat B. Each rat was artificially ventilated with O2, the chest was opened, and both subclavian arteries were ligated. The distribution of blood flow was verified by the microsphere technique. Prior to ligation of the subclavian arteries, blood flow from rat A supplied its own brain and both brain hemispheres but not the brain stem of rat B. Following subclavian artery ligation, blood flow from rat A did not supply A's brain, but supplied both hemispheres and the brain stem of rat B. The head of each rat was, therefore, rendered dependent on the carotid arterial blood supply from another rat. The i.v. injection of clonidine (25 micrograms/kg) into rat A significantly increased mean arterial pressure and slightly, but not significantly, decreased heart rate in rat A, whereas it significantly decreased mean arterial pressure and slightly, but not significantly, decreased heart rate in rat B. Conversely, i.v. injection of methoxamine (25 micrograms/kg) in rat A significantly increased mean arterial pressure and decreased heart rate in rat A, and significantly increased mean arterial pressure and slightly, but not significantly, increased heart rate in rat B. Therefore, this rat cross-circulation preparation can be used to separate the central and peripheral cardiovascular actions of drugs.