Hypotensive and sedative effects of clonidine injected into the rostral ventrolateral medulla of conscious rats

Abstract

We examined the effects of clonidine injected unilaterally into the rostral ventrolateral medulla (RVLM) of conscious, unrestrained rats. We also examined whether the local alpha(2)-adrenoceptor mechanism contributed to the action of clonidine injected into the RVLM. Injection of clonidine but not vehicle solution significantly decreased the mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious, unrestrained rats as well as in propofol-anesthetized rats. The frequency of natural behavior was significantly lower after clonidine injection than after vehicle injection. The depressor and sympathoinhibitory responses were significantly larger in the propofol-anesthetized rats than in the conscious rats. Coinjection of a selective alpha(2)-adrenoceptor antagonist, 2-methoxyidazoxan, with clonidine into the RVLM significantly attenuated the depressor, bradycardiac, sympathoinhibitory, and sedative effects of clonidine injected alone. In conclusion, clonidine injected into the RVLM decreased MAP, HR, and RSNA and caused sedation in conscious, unrestrained rats. The action of clonidine in the RVLM was at least partly mediated by alpha(2)-adrenoceptor mechanisms.

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“…Similar cases have been reported previously (55,56). It is speculated that these compounds can easily cross the blood-brain barrier in neonates and cause hypotensive and sedative effects by binding receptors of a specific group in the rostral ventrolateral medulla, to which clonidine also belongs (54,57).…”

Medetomidine, an .ALPHA.2-Adrenergic Agonist, Activates Cardiac Vagal Nerve Through Modulation of Baroreflex Control

“…The rostral ventrolateral medulla has been reported to serve as an important site in mediating the hypotensive and sedative effects of α2-adrenergic agonist. 17 McCallum et al reported that the central sympathoinhibitory effects of α2-adrenoceptor stimulation are augmented by peripheral inhibition of ganglionic transmission. 18 The results obtained from protocol 1 indicate that low-dose medetomidine may induce a vagal-dominant condition through suppression of the cardiac sympathetic nerve without direct activation of the cardiac vagal nerve.…”

Overexpression of Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Causes Long-Term Decrease in Blood Pressure in the Spontaneously Hypertensive Rats

“…12,13 In Vivo Gene Delivery Into the RVLM Before injection of lentiviral vectors, rats received L-glutamate (2 nmol/200 nL) injections through the bilateral guide cannula to establish that the injection site was the pressor area of the ventrolateral medulla. 19 Rats that expressed a rapid pressor response of 20 mm Hg to L-glutamate were used for the study. Animals were divided into 2 groups: control rats received lenti-GFP, and experimental rats received lenti-ACE2 into the bilateral RVLM.…”