Several possibilities may account for the impaired reflex. First, the sensitivity of muscle afferents is directly proportional to interstitial fluid [35, 37]. Therefore, a reduction in plasma volume and interstitial fluid that may occur with caloric restriction [27], bedrest [38, 39], or water immersion [40], may desensitize the mechanoreceptors. However, this seems unlikely since the cardiovascular responses to handgrip following the normocaloric bedrest intervention were similar to control. Second, caloric restriction may modulate central integration of the mechanoreflex, similar to that of central command. Third, reduced caloric/fat intake may decrease adrenergic sensitivity [24] while increasing endothelium-dependent and –independent vasodilation [41]. This may be consistent with the attenuated BP response; however, it would not explain the diminished sympathetic outflow compared to normocaloric conditions.