Dyckman DJ, Sauder CL, Ray CA. Effects of short-term and prolonged bed rest on the vestibulosympathetic reflex. Am J Physiol Heart Circ Physiol 302: H368 -H374, 2012. First published October 21, 2011 doi:10.1152/ajpheart.00193.2011.-The mechanism(s) for post-bed rest (BR) orthostatic intolerance is equivocal. The vestibulosympathetic reflex contributes to postural blood pressure regulation. It was hypothesized that muscle sympathetic nerve responses to otolith stimulation would be attenuated by prolonged head-down BR. Arterial blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), and peripheral vascular conductance were measured during head-down rotation (HDR; otolith organ stimulation) in the prone posture before and after short-duration (24 h; n ϭ 22) and prolonged (36 Ϯ 1 day; n ϭ 8) BR. Head-up tilt at 80°was performed to assess orthostatic tolerance. After short-duration BR, MSNA responses to HDR were preserved (⌬5 Ϯ 1 bursts/min, ⌬53 Ϯ 13% burst frequency, ⌬65 Ϯ 13% total activity; P Ͻ 0.001). After prolonged BR, MSNA responses to HDR were attenuated ϳ50%. MSNA increased by ⌬8 Ϯ 2 vs. ⌬3 Ϯ 2 bursts/min and ⌬83 Ϯ 12 vs. ⌬34 Ϯ 22% total activity during HDR before and after prolonged BR, respectively. Moreover, these results were observed in three subjects tested again after 75 Ϯ 1 days of BR. This reduction in MSNA responses to otolith organ stimulation at 5 wk occurred with reductions in head-up tilt duration. These results indicate that prolonged BR (ϳ5 wk) unlike short-term BR (24 h) attenuates the vestibulosympathetic reflex and possibly contributes to orthostatic intolerance following BR in humans. These results suggest a novel mechanism in the development of orthostatic intolerance in humans. blood pressure; autonomic nervous system; muscle sympathetic nerve activity; hypotension ORTHOSTATIC INTOLERANCE (OI) is the inability to maintain blood pressure and cerebral perfusion while in the upright position. Moreover, the failure to maintain blood pressure in the upright posture is associated with increased mortality (26). Head-down bed rest (BR) is used to simulate microgravity and physical deconditioning and to elicit OI (13). Mechanisms believed to contribute to the development of OI with BR include: impaired vagal baroreflex responses (5), an inadequate increase in sympathetic discharge (18, 42), cardiac atrophy (24), an inability to increase peripheral vascular resistance (3, 25), and hypovolemia (29). Studies indicate that alterations in sympathetic nerve activity contribute to the development of OI (13,18,25,42). Hypotensive episodes during head-up tilt appear to be closely related to lack of increased muscle sympathetic nerve activity (MSNA) (25). MSNA is attenuated during tilt following 14 days of BR in subjects that experienced OI (42). Despite considerable research on this topic, the mechanisms for OI have been an enigma. One possible mechanism for the development of OI after BR that has not been examined is an alteration of the vestibulosympathetic reflex (VSR).Data exist demon...