Sex differences in morphine-induced ventilatory depression reside within the peripheral chemoreflex loop

Background: This study gathers information in humans on the sites of sex-re lated differences in ventilatory depression caused by the mu-opioid recepto r agonist morphine. Methods: Experiments were performed in healthy young men (n = 9) and women (n = 7), Dynamic ventilatory responses to square-wave changes in end-tidal carbon dioxide tension (7.5-15 mmHg) and step decreases in end-tidal oxygen tension (step from 110 to 50 mmHg, duration of hypoxia 15 min) were obtain ed before and during morphine infusion (intravenous bolus dose 100 mu g/kg, followed by 30 mu g . kg(-1) . h(-1)). Each hypercapnic response was separ ated into a fast peripheral and slow central component, which yield central (G(c)) and peripheral (G(p)) carbon dioxide sensitivities. Values are mean @ SD. Results: In carbon dioxide studies in men, morphine reduced G(c) from 1.61 @ 0.33 to 1.23 @ 0.12 l . min(-1) . mmHg(-1) (P < 0.05) without affecting G (p) (control, 0.41 @ 0.16 and morphine, 0.49 @ 0.12 l . min(-1) . mmHg(-1), not significant). In carbon dioxide studies in women, morphine reduced G(c ), from 1.51 @ 0.74 to 1.17 @ 0.52 . min(-1) . mmHg(-1) (P < 0.05), and G(p ), from 0.54 @ 0.19 to 0.39 @ 0.22 l . min(-1) . mmHg(-1) (P < 0.05). Morph ine-induced changes in G(c) were equal in men and women; changes in G(c) we re greater in women. In hypoxic studies, morphine depressed the hyperventil atory response at the initiation of hypoxia more in women than in men (0.54 @ 0.23 vs. 0.26 @ 0.34 l . min(-1) . %(-1), respectively; P < 0.05). The v entilatory response to sustained hypoxia (i.e., 15 min) did not differ betw een men and women. Conclusions: The data indicate the existence of sex differences in morphine -induced depression of responses mediated via the peripheral chemoreflex pa thway, with more depression in women, but not of responses mediated via the central chemoreflex pathway, In men and women, morphine did not change the translation of the initial hyperventilatory response to short-term hypoxia into the secondary decrease in inspired minute ventilation ((V) over dot(i )) caused by sustained hypoxia.