Before flight, low vascular resistance in female astronauts is not associated with lower sympathetic responsiveness, as their supine and standing norepinephrine levels are similar to those of men. This suggests that the gender differences may lie in the responsiveness of the vasculature itself. Premenopausal women appear to have greater endothelium-dependent venodilatory as well as vasodilatory responses than those of men. This suggests that their lower resistance and lower venous return may be nitric oxide-mediated. Many studies have documented hemodynamic changes that occur during and after space flight or bed rest; very few have examined directly vascular responses, fewer still have compared vascular responses in men versus women before and after bed rest, and none has examined both arteries and veins. Therefore, the first purpose of this study was to examine vascular responsiveness in arteries and veins, in women versus men, before and after bed rest.
Important new information emerged in the animal literature that shows that different vascular beds respond differently to simulated microgravity. After male rats are hindlimb-suspended, vessels in their forelimbs undergo hypertrophic remodeling while vessels in their hindlimbs undergo atrophic remodeling. This is thought to occur as a result of the differential changes in transmural pressures and wall shear stress in the fore- and hindlimbs during the suspension. These studies have not been repeated in female rats. Upright humans have more than a 140 mmHg pressure gradient from head to foot. Elimination of this gradient would change the mechanical forces acting on the vasculature in the legs to an even greater extent than in the suspended rats. It is likely that humans in bed rest or space flight would show similar differential regional changes. Since humans are bipedal, both space flight and bed rest would greatly reduce pressures and wall shear stress in the vessels in the legs, but not the arms. Thus atrophic changes would be expected in the vasculature of the legs but not of the arms. This idea has not been pursued in humans, but such changes certainly could contribute to orthostatic hypotension. Therefore, the second purpose of this study was to compare changes in vascular responsiveness in the upper and lower extremities before and after bed rest and relate the findings to the occurrence of orthostatic hypotension.
Female astronauts, as well as a small subset of male astronauts, develop autonomic dysfunction during space flight. In these astronauts, sympathetic responsiveness to orthostatic stress is compromised after flight. Furthermore, both bed rest and space flight studies have shown decreased vagal activity and baroreflex sensitivity, yet these studies have primarily examined male subjects. Therefore, the third purpose of this study was to compare both autonomic and endocrine responses to arterial baroreceptor input in men and women before and after bed rest.
Specific Aim 1:
Compare arterial function in men and women before and after bed rest. It was hypothesized that woman, compared to men, would have greater flow-mediated vasodilation in the brachial and anterior tibial artery and that this gender difference would be exaggerated after bed rest. It was also hypothesized that brachial and anterior tibial artery vasodilation in response to sublingual nitroglycerin will not be different between women and men.
Specific Aim 2:
Compare venous function in men and women before and after bed rest. It was hypothesized that dorsal hand and foot veins of women would dilate more in response to acetylcholine; and constrict more in response to L-NMMA than men, and leg compliance will be greater in women. These gender differences will be exaggerated after bed rest.
Specific Aim 3:
Compare responses in the lower extremity before and after bed rest. Investigators tested the hypothesis that, after bed rest: anterior tibial artery diameter increases will be smaller following ischemia and larger following sublingual nitroglycerin; dorsal foot vein responses to phenylephrine, isoproterenol, acetylcholine and L-NMMA will be smaller after bed rest, and leg compliance will be greater after bed rest.
Specific Aim 4:
Compare responses in the upper extremity before and after bed rest. Investigators tested the hypothesis that, after bed rest: brachial artery diameter increases will be greater following ischemia and smaller following sublingual nitroglycerin; and that dorsal hand vein responses to phenylephrine, isoproterenol, acetylcholine and L-NMMA will be increased after bed rest.
Specific Aim 5:
Tested the hypothesis that women will have a greater loss of neuroendocrine responses to arterial baroreceptor input after bed rest than men.
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Subjects were healthy, normotensive, non-smokers, not obese, taking no medications, and had passed a psychological examination. Female subjects were premenopausal, with regular menses lasting 28 ± 2 days and were studied across the menstrual cycle, starting at menses. Because hormonal changes affect the cardiovascular responses in women, the bed rest study was arranged so that all measurements were taken at the same time in the menstrual cycle (during menses).
The dorsal hand and foot vein and phenylephrine/sodium nitroprusside protocols were performed once during the pre-bed rest period after approximately 8-12 days of diet stabilization, and around bed rest days 30, 60 and 90 days, if applicable. These three protocols were performed on consecutive days. Female subjects were admitted to bed rest such that these test days would fall at the beginning of menstrual cycle. The reactive hyperemia and sublingual nitroglycerin protocols were performed once during pre-bed rest after 6-8 days of diet stabilization, and around bed rest days 7, 21, 31, 49, 60, 75, and during the post-bed rest period on day 0 and 3.
Dorsal vein size in response to bed rest baseline foot vein size was significantly smaller in women compared to men pre-bed rest. By day 60 however, there were no differences in foot vein size such that vein size decreased in the men and women over the course of bed rest. Baseline hand vein size was similar between men and women pre-bed rest and did not change in response to bed rest.
The absolute change in artery diameter from resting to peak diameter following sublingual nitroglycerin administration was greater in the arm than in the leg, changed across bed rest days, and the change across bed rest days was different between the arm and the leg. Similar to previous findings, there was no effect of gender.
Parasympathetic modulation and baroreflex sensitivity decreased with bed rest, with women experiencing a larger decrease in baroreflex sensitivity by day 30 than men. The sympathetic activation of men and parasympathetic responsiveness of women in blood pressure control during physiological stress were preserved throughout bed rest. During PE infusions, women experienced saturation of the R-R interval at high frequency, whereas men did not, revealing a sex difference in the parabolic relationship between high-frequency R-R interval, a measurement of respiratory sinus arrhythmia, and R-R interval. These sex differences in blood pressure control during simulated microgravity reveal the need to study sex differences in long-duration space flight to ensure the health and safety of the entire astronaut corps.
|Mission||Launch/Start Date||Landing/End Date||Duration|
|Campaign 3||02/20/2005||04/14/2010||5 years, 1 month, 25 days|