Muscle Interstitial Calcium during Head-Up Tilt in Humans

Background-During head-up tilt (HUT), peripheral vasoconstriction occurs. This response requires appropriate communication between the sympathetic nerve terminal and vascular smooth muscle cell in the neurovascular space. Both of these cell types require extracellular calcium ([Ca²⁺]_o) for proper activation and function. We hypothesize that [Ca²⁺] _o rises with tilt and in the process contributes to vasoconstriction. Methods and Results-We used microdialysis techniques in the lower-limb skeletal muscle to measure [Ca²⁺]_o changes in this space with HUT. [Ca²⁺]_o was measured in 10 healthy subjects during HUT. We found a 62% increase in the dialysate [Ca²⁺] (0.223±0.018 to 0.353±0.028 mmol/L) with HUT. Conclusions-This result implies a significant increase in [Ca²⁺]_o in the neurovascular space during HUT. This represents the first report of such in situ [Ca²⁺]_o measurements in humans. This rise in [Ca ²⁺]_o may provide a mechanism for proper cell-cell interaction, helping to promote peripheral vasoconstriction during HUT. How this [Ca²⁺]_o transient affects the nerve terminal, vascular smooth muscle cells, or both remains to be determined.