The role of central cholinergic neurons in the maintenance of hypertension

Abstract

Several neurochemical and pharmacological studies have demonstrated a hyperactivity of brain cholinergic neurons in the development and/or maintenance of experimental hypertension. Intravenous (i.v.) administration of physostigmine r~sults in a pressor response of greater magnitude in spontaneously ·4ypertensive (SHR) as . . compared.to age-matched no~motensive (NT} rats. The purpose of this study was to determine. whether this enhanced response is due to dysfunction in presynaptic or postsynaptic compbnents of central cholinergic neurons. The dose-pressor responses.to centrally acting cholinergic agonists were examined in SHR and age-matched NT rats. The response· to i.v. administration of physostigmine, but not arecoline was ·enhanced in SHR compared to NT rats (p<O.Ol). The pressor response to physostigmine, but not.arecoline was greatly reduced in animals following depletion of brain acetylcholine levels. The selective dependence of physostigmine on intact brain cholinergic function as well as its ability to evoke an exaggerated hypertensive response in SHR suggests that presynaptic mechanisms, possibly involving the release of acetylcholine, are responsible for enhanced cholinergic . activiy in SHR rats. In contrast, the pressor response to·intracerebro ventricular (i.c.v.) injection of cholinergic agonists did not result in enhanced hypertensive responses in SHR. Since the pressor response to i.v. injection of physostigmine is mediated at the level of the lower brains~em, and the response to i.c.v. administration is mediated at more rostral brain regions, ~t is concluded that, at least, 2 cholinergic pressor areas exist in the brain, but activation of only one, possibly located in the medulla, results in an enhanced pressor response to central cholinergic stimulation in hypertensive rats.