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Intranasally administered Orexin-A does not activate sympathetic baroreflex function in healthy humans
Background: Orexin-A is a hypothalamic hormone crucially involved in the regulation of sleep/wake states. Orexin-A was previously reported to induce blood pressure (BP) relevant sympathetic activation in animals and orexin-neurons were shown to project towards BP regulating brain structures. In humans intranasal (i.n.) administration has been shown to effectively deliver neuropeptides directly to the central nervous system. In human narcolepsy, a disorder characterized by deficient orexin-A signalling, i.n. orexin-A provided functional effects of sleep architecture. However, sympathetic blood pressure effects remain to be elucidated. Using highly specific microneurographic techniques we investigated, whether i.n. orexin-A would alter sympathetic baroreflex function in healthy humans.
Methods: In a double-blinded cross-over design orexin-A (500 nmol) or placebo (sterile water) was administered i.n. in 12 wake normotensive males. Muscle sympathetic nerve activity (MSNA) was assessed microneurographically and correlated with oscillometric BP and heart rate at supine rest and during pharmacologic baroreceptor challenge before (pre-substance period) and from 30 – 60 minutes after the orexin-A challenge (post-substance period).
Results: Orexin-A did not produce any changes of BP or heart rate comparing pre- vs. post-substance periods as well as orexin-A vs. placebo condition. Moreover, resting MSNA was not increased and sympathetic baroreflex sensitivity was not altered during baroreceptor testing with vasoactive drugs at the respective periods.
Conclusion: In this pilot study we found that i.n. orexin-A at doses previously shown to induce distinct central nervous effects in humans did not alter sympathetic baroreflex function in healthy subjects.