## 4 Discussion
### Sex Differences  
It is generally accepted that women exhibit a lower tolerance to orthostatic stress and hypovoic stimuli [1,3,21]. Specifically, when exposed to LBNP women were shown to exhibit pre-syncopal symptoms earlier than men [3,5,35,36]. For example, in a progressively increasing LBNP protocol women reported pre-syncopal symptoms at \(462\) mmHg\(\cdot\)min compared to \(1070\) mmHg\(\cdot\)min in men. In the present study, employing mild LBNP stimuli (\(<\)150 mmHg\(\cdot\) min), we did not evidence significant changes in ABP but only minor changes in HR, with no differences between males and females, in agreement with previous studies [37]. However, clear evidence of sympathetic vasoconstriction was consistently detected in terms of reduced tissue oxygenation already at \(-10\) mmHg. This effect, quantified in terms of TOI and HHb slope, was significantly larger in males than females in both arms and legs. There are, however, contrasting results in the literature about possible gender differences in the extent of peripheral vasoconstriction. Converting [2] reported a higher decrease in forearm vascular conductance (FVC) in women than men exposed to progressive LBNP; the difference remained even when changes in vascular conductance were related to changes in central venous pressure (CVP). With a similar protocol, [PERSON] et al. reported, instead, absence of differences in \(\Delta\)FVC/\(\Delta\)CVP up to \(-20\) mmHg [5]; however, in their figure, women appear to reach the minimum FVC already at \(-20\) mmHg, while males progressively decreased FVC up to \(-90\) mmHg, thus demonstrating a stronger vasoconstrtictive capacity. Interestingly, [PERSON] et al. [38] reported a higher vasoconstrtictor response in a group including trained and untrained women compared to men, who, however, also exceptionally exhibited higher tolerance than men. On the other hand, several studies reported larger constrictor responses in men in both the upper [7] and lower limbs [4, 6, 34]. In addition, women appeared to have a reduced myogenic constrictor response in limbs exposed to negative pressure [29] and lower muscle sympathetic nerve activity in response to LBNP [21]. In the cited studies, blood flow measurements, generally based on venous occlusion plethysmography, may be difficult to interpret, given the need to account for differences in body weight, tissue composition, etc. In this respect, the presently observed decrease in tissue oxygenation, reflecting the increased Hb desaturation, may better represent the actual hypoperfusion undergone by the tissues. Our data support the concept that males have a more prominent capacity to reduce peripheral blood flow, which may contribute to their generally observed greater tolerance to LBNP.  
As for blood pooling in the legs, a number of studies have reported increased pooling in males compared to females during LBNP [2, 4, 7]. In the present study, NIRS blood volume indices did not evidence any dependence on sex. These data are not in contrast considering that THI and tHb are related to a small cutaneous-muscular sample volume which is not representative of the entire limb and that the largest blood volume changes occur at the level of the large veins [28].