Pharmacological evidence for a central alpha-sympathomimetic mechanism controlling blood pressure and heart rate.

Laubie, Michel; Delbarre, B; Bogaievsky, Dominique; Bogaievsky, Y.; Tsoucaris-Kupfer, Danita; Senon, D.; Schmitt, H

doi:10.1161/01.res.38.6.35

Cited by 35 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The findings we report here are consistent with the sympathoinhibitory effects reported previously 6 for clonidine, a centrally acting a 2 adrenergic receptor agonist that is thought to act, in part, by potentiating the arterial baroreflexes. Thus, our results are consistent with those that showed an augmented gain of the baroreflex control of the heart rate following clonidine administration.…”

Section: Discussionsupporting

confidence: 92%

Central effect of intravenous phenylephrine on baroreflex control of renal nerves.

Imaizumi¹,

Brunk²,

Gupta³

et al. 1984

Hypertension

View full text Add to dashboard Cite

SUMMARY Responses of renal sympathetic nerve activity were determined in eight chloraloseanesthetized rabbits during sustained (1-3 minutes) increases in arterial pressure induced by phenylephrine infusion, and as arterial pressure returned to control. In four of the eight experiments, aortic baroreceptor traffic was also recorded. When arterial pressure was raised from 81 ± 5 to 110 ± 7 mm Hg, renal nerve activity decreased from 30 ± 7 to 1 ± 1 imp/sec. Aortic nerve activity increased from 208 ± 35 to 346 ± 49 imp/sec. When pressure returned to control (81 ± 5 mm Hg), renal nerve activity remained inhibited (7 ± 2 imp/sec), even though aortic nerve activity had also returned to control (195 ± 33 imp/sec). Arterial pressure and traffic in the renal and aortic nerves returned to control over the succeeding 1 to 5 minutes. Transient increases in arterial pressure (lasting less than 1 minute) due to bolus injections of phenylephrine resulted in inhibition of renal nerve traffic followed by rapid recovery. In five rabbits with aortic and vagal nerves sectioned and both carotid sinuses isolated from the circulation, intravenous phenylephrine infusion augmented the gain of the isolated carotid baroreflex (particularly at low carotid sinus pressures). In nine experiments, injection of phenylephrine (0.01, 0.1, or 1.0 /xg) into the lateral ventricles did not change the basal renal nerve traffic but augmented the gain of the baroreflex control of the renal nerves. Our data indicate that peripherally infused phenylephrine can alter the arterial baroreflex control of the renal nerves by a central effect. The similar influence of intracerebroventricular phenylephrine on baroreflex control of the renal nerves is consistent with this view. (Hypertension 6: 906-914, 1984) KEY WORDS • phenylephrine • rabbits • carotid baroreflex • vagi intracerebroventricular • alpha aderenergic receptors I NCREASES in arterial pressure augment the discharge of arterial baroreceptors and result in baroreflex inhibition of sympathetic nerve activity.1 When pressure returns from an elevated level toward the control level, the arterial baroreceptor discharge decreases. In fact, because of hysteresis effects, one would expect less baroreceptor discharge at a given pressure when the pressure was falling than when it was rising.2 Thus, the expected reflex response would be that, as the pressure returned to control, sympathet-

show abstract

Section: Discussionsupporting

confidence: 92%

Central effect of intravenous phenylephrine on baroreflex control of renal nerves.

Imaizumi¹,

Brunk²,

Gupta³

et al. 1984

Hypertension

View full text Add to dashboard Cite

show abstract

“…Thus, clonidine appears to lower blood pressure by an action on the medulla oblongata or the pons. The results confirm the reports of Saltier and Van Zweiten [22] and Katie et al [12], Additional evidence for a medullary or pontine site of action on blood pressure is the report that large lesions in the ventral medulla prevent the hypotensive response to clonidine [14] and the report that local injections of clonidine into the region of the motor nucleus of the vagus or the medullary reticular for mation also decrease blood pressure [23],…”

Section: Discussionsupporting

confidence: 88%

“…Thus it may be that 2 //g/kg is too large a dose to demonstrate a selective effect. Lattbie et al [14] have presented evidence that clonidine acts at different sites to produce decreases in sympathetic dis charge and it is possible that clonidine could be acting at several different sites to affect heart rate.…”

Section: Discussionmentioning

confidence: 99%

Sites at which Clonidine Acts to Affect Blood Pressure and the Secretion of Renin, Growth Hormone and ACTH

Rudolph¹,

Kaplan²,

Ganong³

1980

Neuroendocrinology

View full text Add to dashboard Cite

To further define the sites in the brain at which clonidine acts to lower blood pressure, inhibit renin secretion, inhibit ACTH secretion, and stimulate growth hormone secretion, small doses of this drug were infused into the vertebral arteries, into the carotid arteries and intravenously in pentobarbital-anesthetized dogs. Because injections of radioactive microspheres demonstrated that vertebral blood reached the hypothalamus, intravertebral and intracarotid infusions were also carried out after occlusion of the basilar artery in the midpontine region. Intracarotid clonidine, 2 μg/kg, decreased plasma ACTH and corticoids and increased plasma growth hormone, whereas the same dose had no effect on these hormones when given intravenously or when given intravertebrally after occlusion of the basilar artery. Intravertebral clonidine lowered blood pressure to a greater degree than intracarotid and intravenous clonidine. The reduction in heart rate produced by clonidine was essentially the same whether the drug was administered via the intravenous, intracarotid, or intravei tebral route. Intracarotid and intravertebral clonidine decreased plasma renin activity whereas in this dose intravenous clonidine did not. However, there was no renin response to intracarotid and intravertebral clonidine when the basilar artery was occluded. The data support the conclusion that clonidine acts rostral to the pons to decrease ACTH secretion and increase growth hormone secretion, whereas it acts on the medulla or adjacent hindbrain to lower blood pressure. In the dose used, clonidine appears to affect heart rate by a peripheral rather than a central action. The data confirm the observation that clonidine acts on the brain to inhibit renin secretion, and establish that the renin-inhibiting site is different from the blood pressure-lowering site. However, they do not permit localization of the renin-lowering site within the brain.

show abstract

“…clonidine is due to a central effect which decreases arterial blood pressure and heart rate via an inhibition of sympathetic nerve activity (Schmitt et al, 1973). This action has been localized at the level of the medulla (see, Laubie et al, 1976) and more precisely the site of action has been demonstrated to be located in the rostral ventrolateral medulla (Bousquet et al, 1981;Sun & Guyenet, 1986). a2-Adrenoceptors have been implicated in this central action of clonidine (Schmitt, 1977;Timmermans et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

A comparative study of the reversal by different α₂‐adrenoceptor antagonists of the central sympatho‐inhibitory effect of clonidine

Vayssettes-Courchay

Bouysset

Cordi

et al. 1996

British J Pharmacology

View full text Add to dashboard Cite

1 The recovery of the clonidine-induced hypotension, bradycardia and sympatho-inhibition produced by several putative o2-adrenoceptor antagonists was investigated in pentobarbitone anaesthetized rats. The activity of four substances containing an imidazoline structure: idazoxan, methoxy-idazoxan, BRL44408 and atipamezole was compared with the effect of fluparoxan, yohimbine and L-657,743; in addition the effect of the ac-adrenoceptor antagonist, prazosin, was also studied. 2 Prazosin (0.03-1 mgkg-1, i.v.) failed to alter the sympatho-inhibitory and hypotensive effects of clonidine (10 ,ug kg'-, i.v.). L-657,743 (0.01-1 mg kg-', i.v.) induced a recovery of blood pressure, heart rate and renal sympathetic nerve activity. Yohimbine (0.03-3 mg kg-1, i.v.) completely reversed the sympatho-inhibitory effect of clonidine but did not alter its hypotensive effect. 3 The four imidazoline drugs: idazoxan (10-300 ,ug kg-1, i.v.), methoxy-idazoxan (1-100 mug kg 1, i.v.), BRL44408 (0.1-3 mg kg-1, i.v.) and atipamezole (0.03-1 mg kg-', i.v.) and fluparoxan (10-300 jg kg-1, i.v.) reversed the clonidine-induced hypotension but produced only a partial recovery of the renal sympathetic nerve activity and of the heart rate. After pretreatment with prazosin (0.1 mg kg-', i.v.), the recovery of the sympathetic nerve activity elicited by these compounds was significantly higher. In hexamethonium (10 mg kg-1, i.v.) pretreated rats, these five drugs induced dose-related hypertension which was reduced by pretreatment with prazosin (0.1 mg kg-1, i.v.). 4 Our results indicate that the putative CX2-adrenoceptor antagonists idazoxan, methoxy-idazoxan, BRL44408, atipamezole and fluparoxan also have a peripheral hypertensive effect which is mediated through activation of vascular a1-adrenoceptors; this property of the compounds may be partly responsible for the reversal of the hypotensive action of clonidine. Considering the structure and the affinities of the drugs tested, our data indirectly suggest that a2A-adrenoceptors may be implicated in the central sympatho-inhibitory effects of clonidine.

show abstract

Pharmacological evidence for a central alpha-sympathomimetic mechanism controlling blood pressure and heart rate.

Cited by 35 publications

References 0 publications

Central effect of intravenous phenylephrine on baroreflex control of renal nerves.

Central effect of intravenous phenylephrine on baroreflex control of renal nerves.

Sites at which Clonidine Acts to Affect Blood Pressure and the Secretion of Renin, Growth Hormone and ACTH

A comparative study of the reversal by different α₂‐adrenoceptor antagonists of the central sympatho‐inhibitory effect of clonidine

Contact Info

Product

Resources

About

Pharmacological evidence for a central alpha-sympathomimetic mechanism controlling blood pressure and heart rate.

Cited by 35 publications

References 0 publications

Central effect of intravenous phenylephrine on baroreflex control of renal nerves.

Central effect of intravenous phenylephrine on baroreflex control of renal nerves.

Sites at which Clonidine Acts to Affect Blood Pressure and the Secretion of Renin, Growth Hormone and ACTH

A comparative study of the reversal by different α2‐adrenoceptor antagonists of the central sympatho‐inhibitory effect of clonidine

Contact Info

Product

Resources

About

A comparative study of the reversal by different α₂‐adrenoceptor antagonists of the central sympatho‐inhibitory effect of clonidine