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

Abstract

Treatment of rats for 4 days with α-methyldopa, 200 mg/kg/day i.p., increases steady state levels of proopiomelanocortin (POMC) mRNA in the mediobasal hypothalamus, as measured by DNA excess solution hybridization. The increase is prevented by parallel treatment with yohimbine, 2 mg/kg/day i.p., but not by naltrexone, 2 mg/kg/day i.p. Treatment with the peripheral vasodilator hydralazine, 2 mg/kg/day, does not affect POMC mRNA levels. In situ hybridization histochemistry with a cRNA probe for POMC indicates that POMC-containing cells are located within the confines of the arcuate nucleus both in control and in α-methyldopa-treated rats, and confirms the increase in POMC mRNA in the latter. Microinjection of 2 µg of α-methylnorepinephrine unilaterally into the arcuate nucleus of urethane-anesthetized rats causes hypotension and bradycardia, which can be inhibited by 200 ng of yohimbine microinjected into the same site, or by 100 ng l-naloxone microinjected into the ipsilateral nucleus tractus solitarii, but not into the arcuate nucleus. These findings are interpreted to indicate that activation of α₂-adrenergic receptors located on POMC-containing neurons in the arcuate nucleus causes β-endorphin release and stimulation of opiate receptors in the NTS, which results in hypotension and bradycardia, and that this mechanism contributes to the hypotensive action of α-methyldopa.

Melanocortin Antagonists Define Two Distinct Pathways of Cardiovascular Control by α- and γ-Melanocyte-Stimulating Hormones

“…In agreement with published observations (Petty and De Jong, 1982;Mosqueda-Garcia and Kunos, 1987;Li et al, 1996), unilateral microinjection of 1 pmol of ␤-endorphin into the DVC also caused long-lasting hypotension and bradycardia (Fig. 2).…”

“…Earlier studies have established that activation of POMC-containing neurons in the arcuate nucleus causes hypotension and bradycardia via the release of ␤-endorphin and subsequent activation of opiate receptors in the medullary DVC (Mosqueda-Garcia et al, 1986;Mastrianni et al, 1989) and that this pathway may be involved in the action of certain centrally acting antihypertensive agents (Kunos et al, 1981;Van Giersbergen et al, 1989;Li et al, 1996). The hypotension and bradycardia elicited by electrical stimulation of the arcuate nucleus were eliminated by ipsilateral deafferentation of the DVC but were inhibited only partially by intra-DVC microinjection of naloxone or a ␤-endorphin antiserum (Mastrianni et al, 1989).…”

Epigenomic and metabolic responses of hypothalamic POMC neurons to gestational nicotine exposure in adult offspring

“…These included the dopamin receptor [56], oxytocin receptor [57], metabotropic glutamate receptor I-III [58, 59], ionotropic glutamate receptor, histamine H1/H2 receptor [60], serotonin 1–4 (5HT1-4) receptor [61], GABA-B receptor II [62, 63], α-adrenoceptor [64], β1-3 adrenoceptor, and muscarinic acetylcholine receptor 1–4 pathways [65] (Fig. 6; Table 7; Additional file 2: Table S2).…”

Expression of c-Fos in arcuate nucleus induced by electroacupuncture: Relations to neurons containing opioids and glutamate

“…Stimulation of proopiomelanocortin (β-endorphin precursor)-containing neurons in the ARC causes opioid-mediated hypotension (Li et al, 1996). These results suggest that opioids-containing neurons in the ARC might regulate sympathetic outflow and the hemodynamic responses to EA (Li et al, 1996).…”