| Abstract Chapter 2. Activation of the vestibular otolith organs with head-down rotation increases muscle sympathetic nerve activity (MSNA) in humans. Previously, we demonstrated this vestibulosympathetic reflex (VSR) elicits increases in MSNA during baroreflex unloading (i.e., lower-body negative pressure) in humans. Whether such an effect persists during baroreflex loading is unknown. We tested the hypothesis that the ability of the VSR to increase MSNA is preserved during baroreflex unloading and inhibited during baroreflex loading. Ten subjects (26+/-1 yr) performed 3 trials of head-down rotation (HDR) to activate the VSR. These trials were performed after a period of sustained saline (control), nitroprusside (baroreflex unloading: 0.8-1.0 mug/kg/min), and phenylephrine (baroreflex loading: 0.6-0.8 mug/kg/min) infusion. Nitroprusside infusion decreased (Delta7+/-1 mmHg; p<0.001) and phenylephrine infusion increased (Delta8+/-1 mmHg; p<0.001) mean arterial pressure at rest. HDR performed during the control (Delta3+/-2 bursts/min, Delta314+/-154 arbitrary units (au) total activity, Delta41+/-18% total activity; p<0.05) and nitroprusside trials (Delta5+/-2 bursts/min, Delta713+/-241 au total activity, Delta49+/-20% total activity; p<0.05) increased MSNA similarly despite significantly elevated levels at rest (13+/-2 to 26+/-3 bursts/min) in the latter. In contrast, HDR performed during the phenylephrine trial failed to increase MSNA (Delta0+/-1 bursts/min, Delta-15+/-33 au total activity, Delta-8+/-21% total activity). These results confirm previous findings that the ability of the VSR to increase MSNA is preserved during baroreflex unloading. In contrast, the ability of the VSR to increase MSNA is abolished during baroreflex loading. These results provide further support for the concept that the VSR may act primarily to defend against hypotension in humans.;Abstract Chapter 3. Orthostatic intolerance is a common problem following bed rest. The mechanism for this is equivocal. Vestibular reflexes contribute to orthostatic blood pressure regulation. We hypothesized that sympathetic nerve responses to otolith stimulation would be attenuated by prolonged head-down bed rest (HDBR) and that this attenuation would be associated with increased orthostatic intolerance. 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-hrs; n=22) and prolonged (36+/-1 days; n=8) HDBR. Head-up tilt at 80° was performed to assess orthostatic tolerance. After short-duration HDBR, MSNA responses to HDR were preserved (Delta5+/-1 bursts/min, Delta53+/-13% burst frequency, Delta65+/-13% total activity; p<0.001). No association was observed between the vestibulosympathetic reflex and head-up tilt duration. After prolonged HDBR, MSNA responses to HDR were attenuated ∼50%. MSNA increased by Delta23+/-13% burst frequency and Delta34+/-22% total activity during HDR. Moreover, these results were observed in 3 subjects tested again at 75+/-1 days of HDBR. This reduction in MSNA responses to otolith organ stimulation at 5 weeks was associated with reductions in head-up tilt duration. These results indicate that prolonged HDBR (∼5 wks) attenuates the vestibulosympathetic reflex and contributes to orthostatic intolerance following HDBR in humans. These results suggest a novel mechanism in the development of orthostatic intolerance in humans.;Abstract Chapter 4. Classically, the glycerol dehydration test (GDT) has been used to test for the presence of Meniere's disease and can cause acute alterations in vestibular reflexes in both normal and pathological states. The vestibulosympathetic reflex (VSR) elicits increases in muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction. We hypothesized that the GDT would attenuate the VSR through an acute fluid shift of the inner ear. Nine male subjects (27+/-1 years) performed head-down rotation (HDR), which engages the VSR, before and after administration of either the GDT or saline. MSNA (microneurography), arterial blood pressure, and leg blood flow (venous occlusion plethysmography) were measured during HDR. Before drug administration, HDR significantly increased MSNA in burst frequency (Delta5+/-1 bursts/min, Delta8+/-1 bursts/min; p<0.01) and total activity (Delta44+/-13%, Delta77+/-17%; p<0.01), and decreased calf vascular conductance (Delta15+/-6%, Delta20+/-3%; p<0.01), in both the saline and glycerol trials, respectively. Post-saline, HDR still significantly increased MSNA (Delta6+/-2 bursts/min, Delta83+/-20% total activity; p<0.01) and decreased calf vascular conductance (Delta21+/-4%, p<0.01), which was not significantly different from pretesting. In contrast, post-GDT resulted in an attenuation of MSNA (Delta3+/-1 bursts/min, Delta22+/-3% total activity) and reduction in calf vascular conductance (Delta7+/-4%) during HDR. These results suggest that a fluid shift of the inner ear via glycerol dehydration attenuates the VSR. These data provide support that dynamic fluid shifts can have a significant effect on the VSR. |
