Peripheral opiate receptors are not involved in the naloxone-sensitive cardiovascular effects of clonidine in rats

doi:10.1016/0006-8993(88)91438-2

Brain Research

Volume 442, Issue 1, 23 February 1988, Pages 119-123

https://doi.org/10.1016/0006-8993(88)91438-2 Get rights and content

Abstract

The cardiovascular effects of clonidine and their inhibition by naloxone or naloxone methylbromide were tested in urethane-anesthetized, normotensive Sprague-Dawley rats. Clonidine administered intravenously (5 μg/kg) or directly into the nucleus tractus solitarii (NTS, 5 nmol) caused hypotension and bradycardia. The effects of intra-NTS clonidine were dose-dependently inhibited by intra-NTS administration of either antagonist, naloxone being 10 times more potent than naloxone methylbromide. The effects of i.v. clonidine were significantly inhibited by 2 mg/kg of i.v. naloxone, but were unaffected by 20 mg/kg of i.v. naloxone methylbromide. Naloxone alone had no effect on blood pressure or heart rate when given either centrally or systematically, whereas naloxone methylbromide given i.v., but not intra-NTS caused transient hypotension and tachycardia. It is concluded that central but not peripheral opiate receptors are involved in the cardiovascular effects of clonidine.

References (22)

T.M. Argentieri et al.
Interaction of the opiate antagonist, naltrexone methyl bromide, with the acetylcholine receptor system of the motor and plate
Brain Research
(1983)
D.R. Brown et al.
The use of quaternary narcotic antagonists in opiate research
Neuropharmacology
(1985)
L.E. Eiden et al.
Enkephalins modulate the responsiveness of rat atria in vitro to norepinephrine
Peptides
(1982)
J. Knoll
Neuronal peptide (enkephalin) receptors in the ear artery of the rabbit
Eur. J. Pharmacol.
(1976)
R.E. Lang et al.
Evidence for the presence of enkephalins in the heart
Life Sci.
(1983)
J.R. Naranjo et al.
β-Endorphin: a common factor in the antihypertensive action of clonidine-type imidazolines in spontaneously hypertensive rats
Gen. Pharmacol.
(1985)
M.A. Petty et al.
Endorphins and the hypotensive response to stimulation of alpha-receptors in the brain stem by alpha-methylnoradrenaline
Neuropharmacology
(1984)
D.J. Pettibone et al.
Clonidine releases immunoreactive β-endorphin from rat pars distalis
Brain Research
(1981)
A. Ronai et al.
〈Met⁵〉enkephalin-Arg-Phe acts on vascular opiate receptors
Eur. J. Pharmacol.
(1982)
C. Farsang et al.
Naloxone reverses the antihypertensive effect of clonidine
Br. J. Pharmacol.
(1979)

J.W. Holaday

Cardiovascular effects of endogenous opiate systems

Annu. Rev. Pharmacol. Toxicol.

(1983)

Cited by (6)

Significance of an opiate mechanism in the adjustment of cerebrocortical oxygen consumption and blood flow during hypercapnic stress
1992, Brain Research
The role of adrenal medulla-derived enkephalins in the control of hypercapnic cerebrocortical blood flow (CBF) and oxygen consumption (CMRO₂) was investigated in the ketamine anesthetized rat. Three experimental interventions were utilized: inhibition of opioid receptors with naloxone, decrease of adrenal enkephalin production with chronic adrenal medullectomy, and treatment of adrenal demedullated animals with the synthetic enkephalin analog,d-Ala²,N-Me-Phe⁴, Gly⁵ -ol-enkephalin (DAGO). In intact, untreated animals hypercapnia increased CBF and CMRO₂ by approximately 300 and 35%, respectively. Naloxone reduced the hypercapnic increase of CBF, and transformed the hypercapnic increase of CMRO₂ into a decrease. The mid-points of the dose-response curves for (1)-naloxone and (d)-naloxone were 10 μg/kg and 100 μg/kg, respectively. Adrenal demedullation and treatment with (1)-naloxone (0.2 mg/kg) decreased the hypercapnic CBF and CMRO₂ by approximately 50%. DAGO treatment of adrenal demedullated animals restored the hypercapnic CBF and CMRO₂ to values similar to those found in intact animals. These observations suggest that opioid peptides (most likely adrenal medulla-derived enkephalins) play a significant role in the regulation of CMRO₂ and CBF during moderate hypercapnia.
Participation of opiate receptors located in the nucleus tractus solitarii in the hypotension induced by α-methyldopa
1989, Brain Research
The local administration of the opiate receptor antagonist,naltrexone, into the nucleus tractus solitarii (NTS) inhibited the hypotension induced by systemically injected α-methyldopa in conscious rats. In addition, the local injection into the NTS of a β-endorphin antiserum but not of antisera against [Met⁵]enkephalin and dynorphin A (1–13) prevented the α-methyldopa-induced hypotension. These results suggest a role of opiate receptors in the NTS, or in a closely located medullary site, in the centrally mediated hypotension induced by α-methyldopa.
Activation of brainstem endorphinergic neurons causes cardiovascular depression and facilitates baroreflex bradycardia
1989, Neuroscience
The effects of electrical stimulation of the arcuate nucleus on blood pressure, heart rate and baroreflex sensitivity were studied in urethane-anesthetized Sprague-Dawley rats. Stimulation of the mid-anterior parts of the arcuate nucleus at 80 Hz, 0.8 ms and 50–200 μA caused a biphasic, depressor/ pressor, response and moderate bradycardia. Intravenous administration of a vasopressin V₁-receptor antagonist eliminated the pressor component and unmasked a pure depressor response. This depressor response could be inhibited by naltrexone, 2 mg/kg i.v., by an antiserum against β-endorphin, 100 nl injected directly into the ipsilateral nucleus tractus solitarii, or by deafferentation of the dorsal vagal complex (nucleus tractus solitarii and dorsal vagal nucleus) by an ipsilateral, dorsolateral knife-cut of the medulla oblongata. Stimulation of the arcuate nucleus at currents of 20–40 μA did not influence basal blood pressure or heart rate but potentiated the reflex bradycardia induced by phenylephrine, and this effect was completely blocked by naltrexone.
It is concluded that a β-endorphin-containing pathway projecting from the arcuate nucleus to the ipsilateral dorsal vagal complex is involved in depressor cardiovascular regulation and in the facilitation of baroreflex bradycardia.
The peripheral action of clonidine analog ST-91: Involvement of atrial natriuretic factor
1997, Journal of Pharmacology and Experimental Therapeutics
Possible involvement of brain opioid peptides in clonidine-induced hypotension in spontaneously hypertensive rats
1989, Hypertension
Endogenous opioid involvement in the cardiovascular effects of clonidine in rats: Role of the parasympathetic nervous system
1988, Clinical and Experimental Hypertension

View full text

Research reportPeripheral opiate receptors are not involved in the naloxone-sensitive cardiovascular effects of clonidine in rats

Abstract

Brain Research

Neuropharmacology

Peptides

Eur. J. Pharmacol.

Life Sci.

Gen. Pharmacol.

Neuropharmacology

Brain Research

Eur. J. Pharmacol.

Naloxone reverses the antihypertensive effect of clonidine

Br. J. Pharmacol.

Cardiovascular effects of endogenous opiate systems

Annu. Rev. Pharmacol. Toxicol.

Research report
Peripheral opiate receptors are not involved in the naloxone-sensitive cardiovascular effects of clonidine in rats