Ray, Chester A., and Kevin D. Monahan. Aging, opioid-receptor agonists and antagonists, and the vestibulosympathetic reflex in humans. studies indicate that opioids inhibit the firing rate of vestibular neurons, which are important in mediating the vestibulosympathetic reflex. Furthermore, this inhibition appears to be greater in more mature rats. In the present study, we tested the hypotheses that opioids inhibit the vestibulosympathetic reflex in humans and that endogenous opioids contribute

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... o the age-related impairment of the vestibulosympathetic reflex. These hypotheses were tested by measuring muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate responses to otolith organ engagement during head-down rotation (HDR) in young (24 Ϯ 2 yr old) and older (63 Ϯ 2 yr) subjects before and after administration of either an opioid-receptor antagonist (16 mg naloxone in 9 young and 8 older subjects) or an opioid-receptor agonist (60 mg codeine in 7 young and 7 older subjects). Naloxone did not augment the reflex increase in MSNA during HDR in young (⌬7 Ϯ 2 vs. ⌬4 Ϯ 2 bursts/min and ⌬81 Ϯ 23 vs. ⌬60 Ϯ 24% change in burst frequency and total MSNA before and after naloxone, respectively) or older subjects (⌬2 Ϯ 2 vs. ⌬1 Ϯ 2 burst/min and ⌬8 Ϯ 7 vs. ⌬8 Ϯ 9% before and after naloxone). Similarly, codeine did not attenuate the increase in MSNA during HDR in young (⌬8 Ϯ 1 vs. ⌬7 Ϯ 2 bursts/min and ⌬53 Ϯ 4 vs. ⌬64 Ϯ 16% before and after codeine) or older subjects (⌬6 Ϯ 4 vs. ⌬3 Ϯ 3 bursts/min and ⌬38 Ϯ 21 vs. ⌬33 Ϯ 20%). Mean arterial blood pressure and heart rate responses to HDR were not altered by either naloxone or codeine. These data do not provide experimental support for the concept that opioids modulate the vestibulosympathetic reflex in humans. Moreover, endogenous opioids do not appear to contribute the age-associated impairment of the vestibulosympathetic reflex. autonomic nervous system; blood pressure regulation; otolith organs; naloxone; codeine ANIMAL STUDIES INDICATE THAT the vestibular system reflexively alters sympathetic nerve activity (15, 39) and regional blood flow (18) and contributes critically to orthostatic blood pressure regulation (8, 16) . Consistent with these experimental findings in animals, head-down rotation (HDR) performed in young adults, which engages the otolith organs of the vestibular system, increases muscle sympathetic nerve activity (MSNA) and produces limb vasoconstriction (14, 20, 25, 34) . These findings in young humans are consistent with the concept that vestibular activation contributes to orthostatic blood pressure regulation. Importantly, HDR performed in older healthy subjects elicits an attenuated reflex increase in MSNA and systemic hypotension (21, 27). These latter findings sug-Address for reprint requests and other correspondence: C. A. Ray,