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

Abstract

Summary-Opioid peptide involvement in the fall in blood pressure resulting from stimulation of alpha-receptors in the brainstem has been investigated in the urethane-anaesthetised rat. Unilateral microinjection of alpha-methylnoradrenahne into the nucleus tractus sohtarii (NTS) induced a doserelated fall in blood pressure and heart rate. The depressor response induced by the amine was prevented by pretreatment with naloxone, administered either subcutaneously or directly into the nucleus. Pretreatment with antiserum to beta-endorphin, applied locally, also blocked the depressor response, however a similar dilution of antiserum to met-enkephalin was ineffective in this respect. The local application of phentolamine into the n. tractus solitarii caused an initial fall in both blood pressure and heart rate, and blocked the cardiovascular changes induced by alpha-methylnoradrenaline for at least 90 min. Pretreatment with the alpha-receptor antagonist attenuated the fall in blood pressure produced by microinjection of beta-endorphin. These results suggest that the fall in blood pressure observed after administration of alpha-methylnoradrenaline involves a beta-endorphin-like peptide, a probable site of this interaction being the n. tractus solitarii.

Alpha-2-Adrenergic Activation of Proopiomelanocortin-Containing Neurons in the Arcuate Nucleus Causes Opioid-Mediated Hypotension and Bradycardia

“…suggesting that the effect of naloxone was due to inhibition of opiate ((3-endorphin) receptors at a site in the brainstem. Microinjcction of naltrexone or an antiserum to (3-endorphin into the NTS also inhibited the hypoten sive action of a-methyldopa [39], while intra-NTS mi croinjection of P-endorphin mimicked it [21], suggesting that the site of action was in the NTS. The major source of p-endorphin in the brain is POMC-containing neurons in the arcuate nucleus.…”

“…The role of endogenous opioids was first suggested by the findings that naloxone or naltrexone inhibited the hypotensive and bradycardie actions of clonidine and amethyldopa in rats [19,20], findings that have been con firmed by many laboratories [21,22,25,39,40], Cloni dine and a-methylnorepinephrine were also found to cause the release of ^-endorphin-like immunoreactivity from brainstem slices of spontaneously hypertensive rats [28]. suggesting that the effect of naloxone was due to inhibition of opiate ((3-endorphin) receptors at a site in the brainstem.…”

“…The opioid peptide (3-endorphin, which is derived from POMC, can also increase prolactin [13,14] and growth hormone release [15], and elicit centrally me diated hypotension and bradycardia [16][17][18], similar to the effects of co-receptor agonists. Furthermore, opiate receptor antagonists partially inhibit the hypotension and bradycardia caused by centrally acting oo-receptor ago nists [19][20][21][22][23][24][25], as well as clonidine-induced prolactin [26] and growth hormone release [7,27], Such findings have led us to postulate that ay-adrenergic receptors located on POMC-containing neurons in the arcuate nucleus are tar gets for the hypotensive and bradycardic action of central ly acting ct2-receptor agonists, and that stimulation of these receptors results in the release of p-endorphin and subsequent stimulation of opiate receptors in the NTS [8, 28. 29], As the steady state level of precursor mRNA is considered a sensitive indicator of the activity of peptid ergic neurons [30], in the present study we tested this hypothesis by examining the effects of chronic activation of ot2-receptors on the levels of POMC mRNA in the MBH of rats.…”

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).…”

α‐Methyldopa induces a naltrexone‐insensitive antinociception and hypomotility in rats

“…Kunos and coworkers were the first to report that the opiate receptor antagonist, naloxone, inhibited clonidine-induced hypotension (Farsang & Kunos, 1979) and partially reversed the hypotension induced by amethyldopa (Farsang et al, 1980) in spontaneously hypertensive rats. In normotensive rats, intracisternal (Van Giersbergen & De Jong, 1988) and intra-NTS (Petty & De Jong, 1984) pretreatment with naloxone resulted in an inhibition of the decrease in blood pressure induced by administration via the same route of a-methyldopa and a-methylnoradrenaline, respectively. Since an antiserum against f-endorphin also inhibited a-methyldopa-(Van Giersbergen et al, 1989b) and clonidine-induced hypotension (Ramirez-Gonzalez et al, 1983;Van Giersbergen et al, 1989a), this opioid peptide might be the endogenous ligand for the opiate receptors that are blocked by naloxone.…”