The major findings of this investigation are fivefold: (1) HR at rest and throughout the static handgrip protocol was elevated from bedrest and reduced with caloric restriction; (2) HR and BP responses to handgrip exercise were significantly attenuated following caloric restriction trials, independent of bedrest; (3) MSNA exhibited a blunted response to exercise, but not to post-exercise circulatory arrest (metaboreceptor stimulation), following hypocaloric intake; (4) HR and BP responses after the normocaloric ambulatory and bedrest interventions were identical; and (5) HR following both bedrest trials was significantly greater at rest and throughout cold pressor; however, MSNA and BP responses were well maintained.