Pharmacological Analysis of the Enhanced Pressor Response to Central Cholinergic Stimulation in Spontaneously Hypertensive Rats

Abstract

Abstract-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 deter mine 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 (I.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 I.c.v. arecoline, confirming the postsynaptic site of action of the agonist. Surprisingly, I.c.v. injection of physo stigmine also did not result in an exaggerated pressor response in SHR. In contrast, injection of physostigmine into the cisterna magna did produce an enhanced hyper tensive 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.

IS THE M1‐MUSCARINIC RECEPTOR A CANDIDATE GENE FOR HYPERTENSION IN THE SPONTANEOUSLY HYPERTENSIVE RAT?

“…genetic spontaneously hypertensive rat (SHR) model (Brezenoff & Caputi 1980;Buccafusco & Spector 1980;Buccafusco et al 1990;Scheucher et al 1990). Intracerebroventricular (ICV) administration of hemicholinum-3, which transiently inhibits acetylcholine storage and release, was shown to produce a marked hypotensive response in SHR but not Wistar-Kyoto (WKY) rats (Brezenoff & Caputi 1980;Buccafusco & Spector 1980;Buccafusco et al 1990). Administration of hemicholinum-3 or the selective MI-antagonist, pirenzepine, into the lateral septal area decreased arterial pressure in SHR but not WKY (Scheucher et al 1990).…”

The effect of the acetylcholine transport blocker vesamicol on central cholinergic pressor neurons

“…Using a similar approach, the present study was designed to determine whether Pretreatment with vesamicol in SHR could inhibit the pressor response to central injection of physostigmine and whether such inhibition is related to depletion of brain acetylcholine levels. For the latter series, the medulla and hypothalamus were investigated, since these regions have been demonstrated to mediate the pressor response to central cholinergic stimulation (Giuliano et al, 1989;Punnen et al, 1986;Xiao and Brezenoff, 1988;Buccafusco et al, 1990).…”