Results
The subject clinical characteristics at screening are presented in Table 1. All subjects were young, healthy, normotensive, and nonobese. Subject weights, which were similar at baseline for each intervention, significantly declined following all interventions except control (hypocaloric ambulatory: 79.8 ± 3.6 vs. 78.4 ± 3.7 kg; hypocaloric bedrest: 78.7 ± 3.3 vs. 76.0 ± 3.3 kg; normocaloric bedrest: 78.1 ± 2.8 vs. 76.7 ± 2.8 kg; normocaloric ambulatory: 76.9 ± 3.2 vs. 76.7 ± 3.3 kg).
Table 1 Subject characteristics
Age (years) 24 ± 3
Height (cm) 182 ± 6
Weight (kg) 76 ± 7
BMI (kg/m2) 23 ± 9
Total cholesterol (mmol l−1) 4.2 ± 0.6
HDL (mmol l−1) 1.3 ± 0.3
LDL (mmol l−1) 2.5 ± 0.3
SBP (mmHg) 123 ± 6
DBP (mmHg) 78 ± 8
Values are mean ± SD
BMI body mass index, HDL high density lipoprotein, LDL low density lipoprotein, SBP systolic blood pressure, DBP diastolic blood pressure

Cardiovascular response to handgrip
The time to fatigue during static handgrip was similar following all four interventions (p > 0.05). Hemodynamic measurements before, during, and after handgrip and post-exercise circulatory arrest are presented in Fig. 2. Heart rate was significantly lower at baseline and throughout the protocol following caloric restriction, whereas bedrest was associated with a higher HR. At the same relative forces, HR gradually increased during static handgrip, reached its peak at fatigue, and immediately returned to baseline values during post-exercise circulatory arrest following each intervention. The contraction-induced increases in HR were diminished with caloric restriction (calorie * time interaction p < 0.001). Systolic and diastolic BP (SBP and DBP) increased progressively during static handgrip, peaked at fatigue, and decreased but remained elevated compared to baseline during post-handgrip circulatory arrest. The increase in DBP (Fig. 2) and SBP (Figs. 2 and 3) during handgrip were greatly attenuated with caloric restriction independent of bedrest. Responses were well maintained during post-exercise ischemia.
Fig. 2 Systemic neural and hemodynamic responses to static handgrip and post-exercise muscle ischemia. Data are presented as mean ± SEM. The x-axis during exercise corresponds to the % of time to fatigue. C1 and C2, minutes 1 and 2 of arm cuff occlusion. MSNA is adjusted to minute values and expressed as bursts/min. The main effects calorie, posture, and time are significantly different for HR. Following caloric restriction, the responses of all variables during exercise are attenuated (calorie * time interaction). Values during 2 min of occlusion are similar
Fig. 3 The change in SBP at the point of maximum fatigue. Data are presented as mean ± SEM. The maximum SBP response to static handgrip to fatigue was significantly attenuated following caloric restriction, independent of bedrest

Sympathetic neural response to handgrip
The MSNA responses to static handgrip and post-handgrip circulatory arrest are depicted in Fig. 2 (bottom panel). Data for only hypocaloric and normocaloric ambulatory interventions were analyzed because MSNA was not recorded during the first intervention (involving bedrest). Baseline MSNA was similar; however, the response during static exercise was significantly attenuated with caloric restriction (calorie * time interaction p = 0.04). Burst frequency remained elevated during post-exercise ischemia in both interventions.

Cardiovascular and sympathetic neural responses to cold pressor
Figure 4 shows the hemodynamic and neural responses to the cold pressor test. Heart rate at baseline and during cold pressor was increased with bedrest. As expected, the cold pressor test increased SBP, DBP, and MSNA, and levels returned to baseline following recovery. Heart rate increased during the first minute of the cold pressor test followed by a decline during the second minute and recovery. No differences in sympathetic and pressure responses were identified between any of the interventions.
Fig. 4 Systemic neural and hemodynamic responses to cold pressor test. Data are presented as mean ± SEM. The main effects of posture and time are significantly different for HR, whereas time is significant for BP as well as MSNA