Humans exposed to real or simulated microgravity experience decrements in blood pressure regulation during orthostatic stress that may be related to autonomic dysregulation and/or hypovolemia. We examined the hypothesis that hypovolemia, without the deconditioning effects of bed rest or spaceflight, would augment the sympathoneural and vasomotor response to graded orthostatic stress. Radial artery blood pressure (tonometry), stroke volume (SV), brachial blood flow (Doppler ultrasound), heart rate (electrocardiogram), peroneal muscle sympathetic nerve activity (MSNA; microneurography), and estimated central venous pressure (CVP) were recorded during five levels (Ϫ5, Ϫ10, Ϫ15, Ϫ20 and Ϫ40 mmHg) of randomly assigned lower body negative pressure (LBNP) (n ϭ 8). Forearm (FVR) and total peripheral vascular resistance (TPR) were calculated. The test was repeated under randomly assigned placebo (normovolemia) or diuretic (spironolactone: 100 mg/day, 3 days) (hypovolemia) conditions. The diuretic produced an ϳ16% reduction in plasma volume. Compared with normovolemia, SV and cardiac output were reduced by ϳ12% and ϳ10% at baseline and during LBNP after the diuretic. During hypovolemia, there was an upward shift in the %⌬MSNA/⌬CVP, ⌬FVR/⌬CVP, and ⌬TPR/⌬CVP relationships during 0 to Ϫ20 mmHg LBNP. In contrast to normovolemia, blood pressure increased at Ϫ40 mmHg LBNP during hypovolemia due to larger gains in the %⌬MSNA/⌬CVP and ⌬TPR/⌬CVP relationships. It was concluded that acute hypovolemia augmented the neurovascular component of blood pressure control during moderate orthostasis, effectively compensating for decrements in SV and cardiac output.baroreflex; muscle sympathetic nerve activity; Doppler ultrasound; lower body negative pressure; vascular resistance; spironolactone EXPOSURE TO REAL OR SIMULATED MICROGRAVITY leads to cardiovascular deconditioning with the associated reductions in blood pressure regulation during orthostatic stress. The effect of this deconditioning on baroreflex neurovascular control in humans is not known, and the pathophysiology of postflight difficulties in blood pressure control remains a focus of debate.To maintain adequate blood pressure and cerebral perfusion during orthostatic stress, reflex adjustments occur to increase heart rate (HR) and peripheral vasoconstriction to compensate for a decreased venous return and stroke volume (SV). Primary contributors to the diminished ability to maintain blood pressure in many individuals after spaceflight or bed rest are believed to include reductions in plasma volume (PV) (3, 7, 10, 11), diminished baroreflex control of HR (10, 21), and/or vascular resistance (36,48). From these findings, two separate hypotheses have been proposed to explain difficulties in postural blood pressure control after spaceflight or bed rest.The first hypothesis recognizes the positive correlation between the duration of microgravity exposure and the degree of PV reduction reaching 12-15% or 350-500 ml (3). Hypovolemia leads to larger decreases in both venous return and ...

As with blood pressure, age-related changes in muscle sympathetic nerve activity (MSNA) may differ nonlinearly between sexes. Data acquired from 398 male (age: 39±17; range: 18–78 years [mean±SD]) and 260 female (age: 37±18; range: 18–81 years) normotensive healthy nonmedicated volunteers were analyzed using linear regression models with resting MSNA burst frequency as the outcome and the predictors sex, age, MSNA, blood pressure, and body mass index modelled with natural cubic splines. Age and body mass index contributed 41% and 11%, respectively, of MSNA variance in females and 23% and 1% in males. Overall, changes in MSNA with age were sigmoidal. At age 20, mean MSNA of males and females were similar, then diverged significantly, reaching in women a nadir at age 30. After 30, MSNA increased nonlinearly in both sexes. Both MSNA discharge and blood pressure were lower in females until age 50 (17±9 versus 25±10 bursts·min −1 ; P <1×10 −19 ; 106±11/66±8 versus 116±7/68±9 mm Hg; P <0.01) but converged thereafter (38±11 versus 35±12 bursts·min −1 ; P =0.17; 119±15/71±13 versus 120±13/72±9 mm Hg; P >0.56). Compared with age 30, MSNA burst frequency at age 70 was 57% higher in males but 3-fold greater in females; corresponding increases in systolic blood pressure were 1 (95% CI, −4 to 5) and 12 (95% CI, 6–16) mm Hg. Except for concordance in females beyond age 40, there was no systematic change with age in any resting MSNA-blood pressure relationship. In normotensive adults, MSNA increases after age 30, with ascendance steeper in women.

To test the hypothesis that head-down-tilt bed rest (HDBR) for 14 days alters vascular reactivity to vasodilatory and vasoconstrictor stimuli, the reactive hyperemic forearm blood flow (RHBF, measured by venous occlusion plethysmography) and mean arterial pressure (MAP, measured by Finapres) responses after 10 min of circulatory arrest were measured in a control trial (n = 20) and when sympathetic discharge was increased by a cold pressor test (RHBF + cold pressor test; n = 10). Vascular conductance (VC) was calculated (VC = RHBF/MAP). In the control trial, peak RHBF at 5 s after circulatory arrest (34.1 +/- 2.5 vs. 48.9 +/- 4.3 ml . 100 ml-1 . min-1) and VC (0.34 +/- 0.02 vs. 0.53 +/- 0.05 ml . 100 ml-1 . min-1 . mmHg-1) were reduced in the post- compared with the pre-HDBR tests (P < 0. 05). Total excess RHBF over 3 min was diminished in the post- compared with the pre-HDBR trial (84.8 vs. 117 ml/100 ml, P < 0.002). The ability of the cold pressor test to lower forearm blood flow was less in the post- than in the pre-HDBR test (P < 0.05), despite similar increases in MAP. These data suggest that regulation of vascular dilation and the interaction between dilatory and constrictor influences were altered with bed rest.