Contribution of pre- and post-synaptic components to heightened central cholinergic activity in spontaneously hypertensive rats.
In several models of essential hypertension in the rat, the pressor response to central cholinergic stimulation is enhanced with respect to age-matched normotensive controls. Neurochemical evidence is available from previous studies to suggest that both pre- (transmitter synthesis and release) and post-synaptic (muscarinic receptors) components of cholinergic transmission may be enhanced in hypertensive rats and that such alterations might be responsible for the exaggerated pressor response to centrally-acting cholinergic agonists. The present study, employing pharmacological approaches, was designed to determine whether pre- or post-synaptic components of central cholinergic transmission were more important in this regard. The pressor response to intravenous injection of the indirect-acting agonist, physostigmine, but not to that of the direct-acting agonist, arecoline, was significantly reduced by pretreatment with hemicholinium-3 (to deplete acetylcholine in brain). The pressor response to physostigmine, but not to arecoline, was enhanced in adult, spontaneously-hypertensive rats, with respect to their normotensive controls. The pressor response to oxotremorine was partially inhibited by pretreatment with hemicholinium-3, but was only partially effective at inducing an exaggerated pressor response in spontaneously hypertensive rats. These results are consistent with the hypothesis that heightened cholinergic activity in spontaneously hypertensive rats is derived primarily through altered pre-synaptic mechanisms, and that the actions of oxotremorine may involve a multi-synaptic cholinergic pathway.
Makari
N F
NF
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2300.
Trimarchi
G R
GR
Buccafusco
J J
JJ
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006426:Hemicholinium 3 / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000503:physiopathology*; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013569:Synapses / Q000502:physiology*
D006426:Hemicholinium 3; D001115:Arecoline; D010095:Oxotremorine; D010830:Physostigmine; D000109:Acetylcholine