Naloxone does not influence cardiovascular responses to mild mental stress in postmenopausal women

Abstract

Litschauer, Brigitte, Georg Schaller, and Michael Wolzt. Naloxone does not influence cardiovascular responses to mild mental stress in postmenopausal women. Am J Physiol Heart Circ Physiol 289: H2120-H2125, 2005. First published July 1, 2005; doi:10.1152/ajpheart.01113.2004The interaction between central opioid activity, sex hormones, and the cardiovascular reactivity to stress is unknown. Twenty-eight healthy postmenopausal women, 16 without, and 12 with hormone replacement therapy (HRT) participated in this randomized, double-blind, cross-over study. The opioid receptor antagonist naloxone or placebo was administered intravenously on 2 different days and mild mental stress was induced by the Stroop Color-Word Test. Cardiovascular responses were assessed noninvasively by impedance cardiography. Stress significantly increased stroke volume, cardiac output, blood pressure, and heart rate, which was not influenced by opioid receptor blockade. Whereas naloxone increased cortisol plasma concentrations irrespective of HRT status, luteinizing hormone concentrations, which were higher in non-HRT compared with HRT women, were increased by naloxone in women with HRT only. These data suggest that the opioidergic tone of the hypothalamus-pituitary-adrenal axis persists in postmenopausal women, irrespective of HRT use, while the opioidergic tone on the hypothalamus-pituitary-gonadal axis seems to depend on an estrogenic milieu. Naloxone does not alter cardiovascular mental stress reactions in postmenopausal women independent of their hormone substitution status.hormone replacement therapy; reactivity; luteinizing hormone; cortisol THE INCIDENCE OF CARDIOVASCULAR diseases (CVD) is lower in premenopausal women compared with men, but this difference is no longer apparent after menopause. While large-scaled randomized trials (37, 42) failed to observe a reduction of cardiovascular events or indicated increased risk for CVD in women on hormone replacement therapy (HRT), several studies suggest a CVD risk reduction (5, 35) and a blood pressurelowering effect (26, 36) of estrogen or estrogen plus progestin HRT in postmenopausal women. Thus HRT and its impact on the cardiovascular system of women are under debate.Cardiovascular responses to mental stress are thought to contribute to the risk for hypertension and coronary atherosclerosis (21). Studies suggest that estrogens also modulate cardiovascular functions during stressful encounters, as premenopausal women are less reactive to psychosocial stressors compared with postmenopausal women and men (3, 31, 33) and estrogen treatment blunts pressor and neuroendocrine responses in postmenopausal women (20,24,27,40). Thus an increased reactivity to mental stress may contribute to the risk of cardiovascular morbidity and mortality after menopause.Endogenous opioids have been implicated in many regulatory functions. Studies have suggested a dampening role of the opioidergic system on cardiovascular stress responses. Activated by mental stress the central opioidergic system is supposed to...

Naltrexone effect on physiological and subjective response to a cold pressor task

“…naloxone, naltrexone) effects on HR and BP have been somewhat inconsistent; however most data suggest that opioid blockade increases epinephrine and cortisol concentrations (al 'Absi et al 2004;Bouloux et al 1985;Bouloux et al 1989;Hughes et al 1991;Litschauer et al 2005;Morris et al 1990). Inconsistent results may perhaps be due to differences related to endogenous opioid levels of those studied.…”

Early life adversity diminishes the cortisol response to opioid blockade in women: Studies from the Family Health Patterns project

“…Second, ELA diminishes both cortisol and heart rate responses to psychological stress [ 3 ]. The present analysis relied on resting measures of cortisol secretion, a time when heart rate levels were stable and unreactive, and therefore no comparison of cortisol and heart rate responses was possible [ 32 ]. Third, the changes in subjective state following naltrexone were greatest in the 0 ELA subjects, the group that presumably had the greatest withdrawal of basal central opioid function following naltrexone, and least in the 3+ ELA group.…”

Estradiol and Mu opioid-mediated reward: The role of estrogen receptors in opioid use

“…We emphasize that the effects of estradiol on hypothalamic opioid activity is conserved across species. For instance, naloxone increases plasma concentrations of luteinizing hormone (LH) in postmenopausal women receiving transdermal or oral estradiol replacement therapy (indicating mediation by endogenous opioids), but not in postmenopausal women not receiving therapy [ 83 ]. The release of LH is regulated by the hypothalamus via gonadotropin-releasing hormone, suggesting that opioid modulation of the HPG axis is under estrogenic control in humans, just as it is in rodents.…”

“…As noted above (reviewed here in Neurobiology of ovarian hormones and endogenous opioids ), both ovariectomy and menopause are associated with lower concentrations of plasma beta-endorphin in women [ 58 , 59 ], and these effects are reversed by estradiol replacement therapy [ 58 , 84 ]. Moreover, the effects of estradiol on endogenous opioid activity have functional consequences, both in terms of regulation of the HPG axis by endogenous opioids [ 83 ] and sensitivity to both the therapeutic and side effects of exogenous mu opioid agonists [ 98 ]. These data are consistent with preclinical studies reporting that estradiol influences opioid receptor tone and alters sensitivity to mu opioid agonists and antagonists (reviewed here in Role of ovarian hormones in preclinical models of opioid use and addiction-related behaviors and following).…”

“…Activation of estrogen receptors increases gene expression for endogenous opioid peptides and mu opioid receptors [ 62 , 155 ]. Activation of estrogen receptors also increases beta-endorphin release [ 52 ], which leads to rapid activation of mu opioid receptors [ 54 , 55 ] and significant but transient consequences across physiological endpoints [ 71 , 83 , 85 ]. These effects can be blocked by acute administration of mu opioid receptor antagonists [ 74 , 85 ] and are mimicked by acute administration of opioid receptor agonists [ 74 ].…”