Naloxone‐induced reversal of clonidine, but not hydralazine, hypotension

Abstract

Bennett, D.A., J.J. DeFeo, E.E. Elko, and L. Harbans: Naloxone reversal of clonidine, but not hydralazine, hypotension. Drug Dev. Res. 2175Res. -179, 1982 Normotensive rats of the Sprague-Dawley strain were administered either the centrally acting hypotensive drug clonidine (0.16 mglkg IP) or the peripherally acting hypotensive drug hydralazine (1.25 rnglkg IP) to induce reliable hypotension (blood pressure reductions of 60-90 mm Hg), as measured by a tail cuff procedure. The opiate antagonist, naloxone (10-20 rnglkg IP), reversed clonidine but not hydralazine hypotension. Naloxone also failed to reverse hydralazine's hypotensive action in rats made hypertensive by renal ligation. Naloxone's reversal of clonidine (0.01 mglkg IV) hypotension was confirmed in experiments in which blood pressure was measured through direct cannulation of the carotid artery. It is suggested that naloxone's antagonism of clonidine hypotension is located at a central nervous system site, and that clonidine hypotension may be mediated through an interaction with the brain opiate systems.

Endorphins and the hypotensive response to stimulation of alpha-receptors in the brainstem by alpha-methylnoradrenaline

“…These authors questioned whether Wistar Kyoto normotensive controls. However Bennett, Defeo, Elko and La1 (1982) were able to show that naloxone antagonised clonidine-induced the study of Farsang and Kunos (1979) differed from the present experiments, since unanaesthetised animals were used and were given alpha-methyldopa intraperitoneally.…”

“…However Bennett, Defeo, Elko and La1 (1982) were able to show that naloxone antagonised clonidine-induced hypotension in normotensive Sprague-Dawley and Long-Evans rats. These authors questioned whether Wistar Kyoto normotensive controls.…”

Endorphinergic mechanism in the central cardiovascular and analgesic effects of clonidine

“…This has suggested that, while the nalsxone-resistent component of the effect of clonidine is generally present, the appearance of an additional, opioid-mediated component may be related to the hypertensive process (Ramirez-Gonzalez et al 1983). However, several other reports have demonstrated naloxone antagonism of the effects of clonidine and a-methylnoradrenaline in various strains of normotensive rats other than WKY (Bennett et al 1982;Hamilton and Longman 2982;Petty and de Jong 1984;Dixon and Chandra 1985;Mosqueda-Garcia et al 1986), as well as in nornlotensive cats (Williams 19859, goats (Eriksson and Traomisto 1983) and, in some studies, nonnotensive humans (Resnick et al 1980;Gremse et al 1986). Furthermore, naloxone antagonism of some noncardiovascular effects of clonidine, such as analgesia (Tchakarov et al 1985) or growth hormone release (Bramnert and Hokfelt 1984), has also been reported.…”

Opiate receptors and the endorphin-mediated cardiovascular effects of clonidine in rats: evidence for hypertension-induced mu-subtype to delta-subtype changes.

“…A growing number of reports indicates, however, that the clonidine-naloxone interaction is present in normotensive rats other than Wistar Kyoto rats (6,(12)(13)(14)(15), as well as in normotensive animals of other species (16)(17)(18), suggesting that the underlying endorphinergic mechanism may have a role in cardiovascular regulation under normal physiological conditions. According to recent evidence, the clonidineinduced release of a P3-endorphin-like peptide, as well as the action of this opioid on opiate receptors occurs in the brainstem nucleus of the nucleus tractus solitarii (NTS) (6,19).…”