Ventrolateral medullary pressor area: site of hypotensive action of clonidine (original) (raw)
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American journal of physiology. Regulatory, integrative and comparative physiology, 2001
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 con...
Site and Mode of Action of Clonidine in the Central Nervous System
Acta Medica Scandinavica, 1977
In urethaneanaesthetized rats clonidine was administered intravenously (i. v.J. intraearebroventricularly (i.c.v.) or onto the surface of the area postrema which protrudes into the fourth cerebnrl ventricle. In each instance clonidine induced a dose-dependent lowering of the blood pressure.
Brain Research, 1987
In vivo electrochemistry allowed recording of a catechol oxidation current in the ventrolateral medulla, caudal to the obex, in anesthetized rats whose ventilatory, metabolic and hemodynamic parameters were rigorously controlled. Hemorrhage or controlled hypotension induced an increase in the metabolism of catecholamines in the A 1 noradrenergic group, which remained activated after full hemodynamic recovery. Clonidine (200/,g. kg-1 i.p.) given 30 min prior to hemorrhage or immediately before controlled hypotension suppressed partially the increased metabolism of catecholamines especially during the recovery period. This suggests that clonidine preserved phasic reactivity upon circulatory disturbances and decreased tonic hyperactivity following circulatory recovery.
Brain Research, 1978
To localize the central site and mechanism of clonidine induced hypotension, the drug was applied by the technique of microiontophoresis to neurons of the bulbar cardiovascular center in decerebrate cats. The excitatory and inhibitory cardiovascular neurons (CVN) were identified by their response to an increase in the arterial blood pressure induced by intravenous injections of small doses of norepinephrine (NE). Clonidine had an inhibitory effect on the spontaneous firing rate of excitatory CVN but had no effect on the firing rate of inhibitory CVN. At the same doses, it had no effect on the firing rate of NCVN recorded from the same area. Furthermore, clonidine had a blocking action on the excitatory response of CVN induced by microiontophoretic application of NE. It is concluded that clonidine produces its hypotensive response by acting on a-adrenergic receptors of bulbar CVN.
The central action of clonidine and its antagonism
British Journal of Pharmacology, 1972
1. We have examined the central actions of clonidine (2-(2-6-dichlorphenylamine)-2-imidazoline hydrochloride). It has been confirmed that when infused into the vertebral artery at 2 ug/min, it caused a decrease in blood pressure and a slight increase in heart rate. The same dose given intravenously or into the carotid artery had no effect. 2. Intravertebral clonidine also greatly reduced the reflex response to carotid occlusion and the effects of an intravertebral infusion of angiotensin (1 ng/kg)/ min. 3. This central action of clonidine was antagonized by the adrenergic neurone blocking drug bethanidine (4-5 mg/kg intravenously) even after the cervical cord had been transected at C4-C6 suggesting that bethanidine also has central actions. 4. Other drugs which also antagonized the central effects of clonidine were guanethidine (4-5 mg/kg intravenously), bretylium (10 mg/kg intravenously) and phentolamine (0-2 mg/kg intravenously). 5. It is suggested that there are central adrenergic neurones which inhibit cardiovascular autonomic reflexes and that the central autonomic effects of clonidine are due to stimulation of inhibitory adrenoceptors. The antagonism by adrenergic neurone blocking drugs of the effect of clonidine could therefore be due to blockade of these inhibitory pathways. 6. The central action of clonidine could only be demonstrated when a high concentration was infused into the vertebral artery and could not be shown with oral doses of (20 tg/kg)/day for seven days. It is concluded that the hypotensive action of therapeutic doses is unlikely to be due to the central action of clonidine.
Journal of Biotechnology Research Center
To examine the hypothesis of a role for α2-adrenoceptors in mediating the mechanism of urethane hypotensive effect whether it's peripheral or central, Wistar rats were anesthetized with urethane or (for comparison) with halothane, to study the influence of urethane that govern the mechanism of central and peripheral α2-adrenoceptors action, on basal BP & HR, and the rise in blood pressure (BP) to the stimulation of caudal pressor area (CPA), when these receptors were either centrally activated by bilateral rostral ventrolateral medulla (RVLM) microinjection of clonidine (30nM), and blockade with any of the clonidine antagonists, yohimbine (500pmol/50nl), and idazoxane (270nM) or yohimbine+idazoxane, or when peripherally activated (of urethane anesthetized rats) by i.v. clonidine (100nmol/kg), which also blockade with idazoxane or yohimbine+idazoxane. The results indicated presence of no anesthetic differences in a partial involvement of α2-receptors-RVLM, vs. a complete involve...
European Journal of Pharmacology, 1986
The present studies examined the role of a 1-versus a2-adrenoceptors in the cardiovascular effects of clonidine administered into the anterior hypothalamic/pre-optic (AH/PO) region of the forebrain by the push-pull perfusion technique. Push-pull cannulas were placed bilaterally into the AH/PO region of anesthetized, paralyzed and ventilated rats. Perfusion of this area with artificial CSF (0.015 ml/min), yohimbine (5 or 50/~M) or prazosin (5 or 50 ~M) for 30 min did not affect mean arterial blood pressure or heart rate. Perfusion of the AH/PO region with clonidine (0.55-5.50 mM) resulted in a concentration-dependent reduction of mean arterial pressure and heart rate. The hypotensive effects of clonidine were found to be greater than the bradycardic effects, when expressed as a percent of pre-infusion baseline values. Co-perfusion with yohimbine (5, 50 laM) significantly attenuated the hypotensive, but not the bradycardic, effects of a single concentration (1.75 mM) of clonidine; this selective antagonism of the hypotensive effect of clonidine by yohimbine was concentration dependent. In contrast to yohimbine, co-perfusion with 5 I~M prazosin did not significantly affect either the clonidine-induced hypotension or bradycardia. Co-perfusion with the higher concentration (50 ~M) of prazosin significantly reversed the bradycardic, but not the hypotensive, effects of 1.75 mM clonidine. These results suggest that AH/PO clonidine perfusion depresses both mean arterial pressure and heart rate, and that the clonidine-induced hypotension is due to a2-adrenoceptor activation, while the clonidine-induced bradycardia is due to al-adrenoceptor activation.
Effect of Clonidine on the Excitability of Vasomotor Loci in the Cat
British Journal of Pharmacology, 1975
The effect of clonidine on the direct excitability of hypothalamic, medullary and spinal vasomotor loci has been investigated in cats anaesthetized with chloralose. 2 Clonidine inhibited the excitability of these loci when it was localized to the central sites by intracerebroventricular, intravertebral arterial or intrathecal injection in very low doses (1-2 jg). 3 Topical application of clonidine (0.01% and 1.0%) to the floor of the fourth ventricle inhibited pressor responses evoked either by stimulation of medullary or hypothalamic vasomotor areas. Inhibition of the pressor responses was accompanied by hypotension and bradycardia in many experiments. 4 It appears that effects of clonidine on the vasomotor loci of the medulla oblongata and the spinal cord contribute to its hypotensive action.
Antihypertensive Effects of Clonidine in Tetraplegic Subjects Devoid of Central Sympathetic Control
Clinical Science, 1979
1. The effects of 300 μg of oral clonidine on blood pressure, heart rate, plasma noradrenaline and adrenaline concentrations were studied in seven tetraplegic subjects with physiologically complete cervical spinal cord transections. 2. Clonidine did not significantly change resting blood pressure during the 8 h of the study. Resting heart rate fell. Resting plasma noradrenaline and adrenaline concentrations, when measured 2 h after clonidine, were not significantly lower. 3. Urinary bladder stimulation resulted in a marked rise in blood pressure accompanied by an elevation in plasma noradrenaline but not adrenaline. The hypertensive response to bladder stimulation was substantially reduced by clonidine, the maximum suppression occurring 2–4 h after administration of the drug. The plasma noradrenaline response to bladder stimulation, when measured 2 h after clonidine, was significantly lower than the response before clonidine. In two tetraplegic subjects with indwelling catheters the...