Pharmacological analysis of the enhanced pressor response to central cholinergic stimulation in spontaneously hypertensive rats.
Central cholinergic pressor neurons exist at several levels of the neuraxis. Activation of these neurons in spontaneously hypertensive rats (SHR) can lead to an exaggerated hypertensive response when compared with normotensive control animals (WKY). Our earlier studies demonstrated that intravenous injection of the indirect acting agonist physostigmine, but not the direct agonist arecoline, resulted in an exaggerated pressor response in SHR. The purpose of this study was to determine whether discrete injection of cholinergic agonists directly into the CNS would also result in an exaggerated pressor response in SHR. Cholinergic pressor neurons in the posterior hypothalamus may be activated following injection of cholinergic agonists into the lateral cerebral ventricles (l.c.v. injection). Cholinergic pressor neurons in the medulla may be activated following injection of agonists into the cisterna magna (i.c. injection). L.c.v. injection of arecoline in freely-moving animals evoked a pressor response in both SHR and WKY rats that was not significantly different between the two strains. Prior depletion of brain acetylcholine with hemicholinium-3 did not affect the pressor response to l.c.v. arecoline, confirming the postsynaptic site of action of the agonist. Surprisingly, l.c.v. injection of physostigmine also did not result in an exaggerated pressor response in SHR. In contrast, injection of physostigmine into the cisterna magna did produce an enhanced hypertensive response in SHR compared to WKY rats. These results are consistent with the presence of two cholinergic pressor systems; however, only the medullary cholinergic system appears to play a prominent role in spontaneous hypertension. Also the hypothalamic (rostral) cholinergic system does not appear to directly interact with the caudal system.
Buccafusco
J J
JJ
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912.
Makari
N F
NF
Hays
A C
AC
D000818:Animals; D001115:Arecoline / Q000494:pharmacology*; D002799:Cholinergic Fibers / Q000187:drug effects; D008297:Male; D010830:Physostigmine / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014666:Vasomotor System / Q000187:drug effects*
D001115:Arecoline; D010830:Physostigmine