Estimations of changes in plasma volume during simulated weightlessness

Results of previous investigations on the effects of simulated microgravity (thermoneutral (34.5 degrees C) head-out water immersion, WI) have indicated that plasma volume (PV) increases initially and thereafter decreases to attain values below the pre-immersion level. In these cases, changes in hematocrit (Hct) and hemoglobin concentration (Hgb) were used as indicators of relative changes in PV. In order to test whether changes in Hct and Hgb are accurate measures of changes in PV during simulated microgravity, direct measurements of PV were performed with a modified Evans blue dye dilution technique before, during, and after a 12 h WI experiment. Furthermore, PV was determined with the same technique before, during, and after acute 6 degrees head-down tilt (HDT). Changes in PV were then compared with changes calculated from changes in Hct and Hgb.     

Rat cardiovascular responses to whole body suspension: head-down and non-head-down tilt.

The rat whole body suspension technique mimics responses seen during exposure to microgravity and was evaluated as a model for cardiovascular responses with two series of experiments. In one series, changes were monitored in chronically catheterized rats during 7 days of head-down tilt (HDT) or non-head-down tilt (N-HDT) and after several hours of recovery. Elevations of mean arterial (MAP), systolic, and diastolic pressures of approximately 20% (P < 0.05) in HDT rats began as early as day 1 and were maintained for the duration of suspension. Pulse pressures were relatively unaffected, but heart rates were elevated approximately 10%. During postsuspension (2-7 h), most cardiovascular parameters returned to presuspension levels. N-HDT rats exhibited elevations chiefly on days 3 and 7. In the second series, blood pressure was monitored in 1- and 3-day HDT and N-HDT rats to evaluate responses to rapid head-up tilt. MAP, systolic and diastolic pressures, and HR were elevated (P < 0.05) in HDT and N-HDT rats during head-up tilt after 1 day of suspension, while pulse pressures remained unchanged. HDT rats exhibited elevated pretilt MAP and failed to respond to rapid head-up tilt with further increase of MAP on day 3, indicating some degree of deconditioning. The whole body suspended rat may be useful as a model to better understand responses of rats exposed to microgravity.     

Baroreceptor-mediated suppression of osmotically stimulated vasopressin in normal humans

Increases in central venous pressure and arterial pressure have been reported to have variable effects on normal arginine vasopressin (AVP) levels in healthy humans. To test the hypothesis that baroreceptor suppression of AVP secretion might be more likely if AVP were subjected to a prior osmotic stimulus, we investigated the response of plasma AVP to increased central venous pressure and mean arterial pressure after hypertonic saline in six normal volunteers. Plasma AVP, serum osmolality, heart rate, central venous pressure, mean arterial pressure, and pulse pressure were assessed before and after a 0.06 ml.kg-1.min-1-infusion of 5% saline give over 90 min and then after 10 min of 30 degrees head-down tilt and 10 min of head-down tilt plus lower-body positive pressure. Hypertonic saline increased plasma AVP. After head-down tilt, which did not change heart rate, pulse pressure, or mean arterial pressure but did increase central venous pressure, plasma AVP fell. Heart rate, pulse pressure, and central venous pressure were unchanged from head-down tilt values during lower-body positive pressure, whereas mean arterial pressure increased. Plasma AVP during lower-body positive pressure was not different from that during tilt. Osmolality increased during the saline infusion but was stable throughout the remainder of the study. These data therefore suggest that an osmotically stimulated plasma AVP level can be suppressed by baroreflex activation. Either the low-pressure cardiopulmonary receptors (subjected to a rise in central venous pressure during head-down tilt) or the sinoaortic baroreceptors (subjected to hydrostatic effects during head-down tilt) could have been responsible for the suppression of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hindlimb suspension training on the central and regional hemodynamic responses during 24 hours antiorthostatic hypokinesia in the awake rat

To date the hindlimb suspension model utilizing rats has a wide application to simulate weightlessness. In our previous study we have examined the cardiovascular responses in the tail suspension model using the radiolabeled microspheres technique. We have reported increases of cardiac output (CO) and decreases of total peripheral vascular resistance (TPVR) after 24 hours of head-down tilt (HDT). However, there is no comparison of arterial and venous systems parameters with blood flow changes in organs and tissues. Apart from the preliminary HDT training influence on these parameters is unknown. Thus we aimed to evaluate the role of HDT training in central circulation responses, venous tone and regional blood flow.     

Influences of prostanoids and nitric oxide on post-suspension hypotension in female Sprague-Dawley rats

Impairment in cardiovascular functions sometimes manifested in astronauts during standing postflight, may be related to the diminished autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, using the 30 degrees head-down tilt (HDT) model, we compared the cardiovascular and biochemical effects of 7 days of suspension and a subsequent 6-h post-suspension period between suspended and non-suspended conscious female Sprague-Dawley rats. Mean arterial pressure (MAP) and heart rate were measured prior to suspension (basal), daily thereafter, and every 2h post-suspension. Following 7 days of suspension, MAP was not different from their basal values, however, upon release from suspension, MAP was significantly reduced compared to the non-suspended rats. Nitric oxide levels were elevated while thromboxane A(2) levels declined significantly in both plasma and tissue samples following post-suspension. The levels of prostacyclin following post-suspension remained unaltered in plasma and aortic rings but was significantly elevated in carotid arterial rings. Therefore, the post-suspension reduction in mean arterial pressure is due mostly to overproduction of nitric oxide and to a lesser extent prostacyclin.     

Peripheral arterial and venous response to tilt test after a 60-day bedrest with and without countermeasures (ES-IBREP)

We quantified the impact of 60-day head-down bed rest (HDBR) with countermeasures on arterial and venous response to tilt. Methods: Twenty-one males: 7 control (Con), 7 resistive vibration exercise (RVE) and 7 Chinese herb (Herb) were assessed. Subjects were identified as finisher (F) or non-finishers (NF) at the post-HDBR 20-min tilt test. The cerebral (MCA), femoral (FEM) arterial flow velocity and leg vascular resistance (FRI), the portal vein section (PV), the flow redistribution ratios (MCA/FEM; MCA/PV), the tibial (Tib), gastrocnemius (Gast), and saphenous (Saph) vein sections were measured by echography and Doppler ultrasonography. Arterial and venous parameters were measured at 3-min pre-tilt in the supine position, and at 1 min before the end of the tilt. Results: At post-HDBR tilt, MCA decreased more compared with pre-HDBR tilt in the Con, RVE, and Herb groups, the MCA/FEM tended to decrease in the Con and Herb groups (not significant) but remained stable in the RVE gr. FRI dropped in the Con gr, but remained stable in the Herb gr and increased in the RVE gr. PV decreased less in the Con and Herb groups but remained unchanged in the RVE gr. MCA/PV decreased in the Con and Herb groups, but increased to a similar extent in the RVE gr. Gast section significantly increased more in the Con gr only, whereas Tib section increased more in the Con and Herb groups but not in the RVE gr. The percent change in Saph section was similar at pre- and post-HDBR tilt. Conclusion: In the Con gr, vasoconstriction was reduced in leg and splanchnic areas. RVE and Herb contributed to prevent the loss of vasoconstriction in both areas, but the effect of RVE was higher. RVE and Herb contributed to limit Gast distension whereas only RVE had a protective effect on the Tib.     

Steep head-down tilt has persisting effects on the distribution of pulmonary blood flow.

Head-down tilt has been shown to increase lung water content in animals and alter the distribution of ventilation in humans; however, its effects on the distribution of pulmonary blood flow in humans are unknown. We hypothesized that head-down tilt would increase the heterogeneity of pulmonary blood flow in humans, an effect analogous to the changes seen in the distribution of ventilation, by increasing capillary hydrostatic pressure and fluid efflux in the lung. To test this, we evaluated changes in the distribution of pulmonary blood flow in seven normal subjects before and after 1 h of 30 degrees head-down tilt using the magnetic resonance imaging technique of arterial spin labeling. Data were acquired in triplicate before tilt and at 10-min intervals for 1 h after tilt. Pulmonary blood flow heterogeneity was quantified by the relative dispersion (standard deviation/mean) of signal intensity for all voxels within the right lung. Relative dispersion was significantly increased by 29% after tilt and remained elevated during the 1 h of measurements after tilt (0.84 +/- 0.06 pretilt, 1.09 +/- 0.09 calculated for all time points posttilt, P < 0.05). We speculate that the mechanism most likely responsible for our findings is that increased pulmonary capillary pressures and fluid efflux in the lung resulting from head-down tilt alters regional blood flow distribution.     

Cardiovascular and hormonal response during a 4-week head-down tilt with and without exercise and LBNP countermeasures

To determine whether exercise and Lower Body Negative Pressure (LBNP) during 28 days of -6 degrees head-down tilt (HDT) would modify orthostatic tolerance and blood volume regulating hormones, twelve healthy men were assigned to either a no- countermeasure (No-CM, n=6), or a countermeasure (CM, n=6) group. LBNP sessions consisted of 15 minutes exposure to -30 mm Hg, on days 16, 18, 20 and 22-28 of HDT. Muscular exercise began on day 8 and consisted of combined graded dynamic and isometric resistance bilateral leg exercise on a specially designed supine ergometer, in two sessions of 15-20 min. each, every day, 6 days per week. A tilt test was performed before and at the end of HDT. Changes in resting plasma volume from control day (D-5) to HDT day 24 were -11.2% for No-CM and -2.2% for CM. After HDT three among the 6 subjects of the No-CM group presented presyncopal or syncopal symptoms, no tilt test was interrupted in CM group. Atrial Natriuretic Peptide (ANP) decreased at day 7 for the two groups and remained low during all the HDT period for No-CM group only. Plasma Renin Activity and Aldosterone increased at day 7 and remained elevated for the two groups. Norepinephrine and epinephrine were unchanged. Elevated diuresis and natriuresis were evident during the first day of HDT. However, renal excretory patterns were different between the two groups: indeed, a decrease of Na+, ANP and cGMP was observed only in No-CM at Day 13 during HDT. Our data showed that the subjects of the No-CM group experienced a greater increase in heart rate and a decrease in systolic blood pressure during tilt tests after HDT; nevertheless, after HDT, blood pressure was better maintained in CM group during the tilt test. The plasma volume decrease measured at the end of HDT was significantly lower in CM group, in contrast, these countermeasures were ineffective in preventing at least certain changes in blood volume regulating hormones.     

Cardiovascular responses to V1-vasopressinergic antagonism in conscious versus anesthetized rats

Experiments were performed to compare the possible effect of endogenous arginine vasopressin on renal hemodynamics between anesthetized, surgically stressed rats and conscious rats. Animals were instrumented with arterial and venous catheters as well as with a pulsed Doppler flow probe on the left renal artery. The rats were studied under the following conditions: (1) conscious and unrestrained; (2) anesthetized only; (3) anesthetized with minor surgical stress; and (4) anesthetized with major surgical stress. Two anesthetic agents were also compared, a mixture of ketamine (110 mg/kg i.m.) and acepromazine (1 mg/kg i.m.), and sodium pentobarbital (50 mg/kg i.p.). Baseline mean arterial blood pressure was significantly higher in pentobarbital-anesthetized rats following surgical stress compared with conscious animals, but blood pressure was not affected by ketamine-acepromazine anesthesia. After baseline measurements of blood pressure, heart rate, and renal blood flow, a specific V1-vasopressinergic antagonist (d(CH2)5Tyr(Me) arginine vasopressin, 10 mg/kg i.v.) was administered to each group. Mean arterial blood pressure, heart rate, and renal blood flow were monitored for an additional 15 min. Mean arterial blood pressure and renal blood flow decreased after V1 antagonism in ketamine-acepromazine-anesthetized rats with major surgical stress, but were not affected in pentobarbital-anesthetized animals. Heart rate and renal vascular resistance were not affected following V1 blockade with either anesthetic agent. These data suggest that arginine vasopressin plays a role in maintaining blood pressure and renal perfusion in ketamine-acepromazine-anesthetized rats following surgical stress, but does not have a significant effect on renal hemodynamics under pentobarbital anesthesia.     

Persistence of tight junctions and changes in apical structures and protein expression in choroid plexus epithelium of rats after short-term head-down tilt

Major alterations of choroidal cell polarity and protein expression were previously shown to be induced in rats by long-term adaptation to space flight (14 days aboard a space shuttle) or anti-orthostatic suspension (14 and 28 days) performed by tilting rats head-down (i.e. using a ground-based model known to simulate several effects of weightlessness). In rabbits, it was hypothesized that the blood-CSF barrier was opened in choroid plexus, after a short head-down suspension. To understand the early responses to fluid shifts induced by head-down tilts and evaluate the tightness of the choroidal junctions, we have investigated the effects of acute adaptations to anti-orthostatic restraints, using hindlimb-suspended Sprague-Dawley and Wistar rats. Ultrastructural and immunocytochemical studies were performed on choroid plexuses from lateral, third and fourth ventricles, after 30, 90 and 180 minutes of head-down tilt. Alterations were not perceptible at the level of choroidal tight junctions, as shown by freeze-fracture, claudin-1 and ZO-1 immunolocalizations and conventional electron microscopy, after intravenous injection of cytochrome C. The apical surface of choroidal cells was clearly more affected. Microvilli were longer and thinner and ezrin was over-expressed during all the periods of time considered, showing an early cytoskeletal response. Several proteins involved in the choroidal production of cerebrospinal fluid (sodium-potassium ATPase, carbonic anhydrase II, aquaporin 1) appeared first increased (30 minutes after the tilt), and then, returned to the control level or were lowered (after a 3-hour head-down suspension). Although head-down tilts do not seem to damage the blood-cerebrospinal fluid barrier in choroid plexus, it seemed that the expression of several apical proteins is affected very early.     

Pulmonary vasodilatory response to neurohypophyseal peptides in the rat.

Experiments were performed on isolated salt-perfused rat lungs to determine the receptor type(s) responsible for the pulmonary vascular effects of the neurohypophyseal peptides arginine vasopressin (AVP) and oxytocin. Bolus administration of AVP to lungs preconstricted with the thromboxane mimetic U-46619 resulted in a dose-dependent vasodilatory response (approximately 65% reversal of U-46619-induced vasoconstriction at the highest dose tested) that was blocked by pretreatment with a selective V1- but not by a selective V2-vasopressinergic receptor antagonist. Administration of a selective V1-agonist to the preconstricted pulmonary vasculature resulted in a vasodilatory response similar to that observed with AVP (approximately 55% reversal of U-46619 vasoconstriction), which was blocked by prior administration of the selective V1-receptor antagonist. Administration of the selective V2-receptor agonist desmopressin to the preconstricted pulmonary vasculature resulted in a small (approximately 8% reversal of U-46619 vasoconstriction) vasodilatory response that was, nevertheless, greater than that produced by addition of vehicle alone and was attenuated by pretreatment with a selective V2-receptor antagonist. Finally, oxytocin also caused vasodilation in the preconstricted pulmonary vasculature; however, the potency of oxytocin was approximately 1% of AVP, and the vasodilation produced by oxytocin was blocked by prior administration of a selective V1-receptor antagonist, suggesting that oxytocin acts via V1-vasopressinergic receptor stimulation. We conclude from these experiments that AVP and oxytocin dilate the preconstricted pulmonary vasculature primarily via stimulation of V1-vasopressinergic receptors. V2-receptor stimulation results in a minor vasodilatory response, although its physiological significance is unclear.     

Effect of lower body negative pressure on orthostatic tolerance and cardiac function during 21 days head-down tilt bed rest

The purpose of the present study was to investigate the changes of orthostatic tolerance and cardiac function during 21 d head-down tilt (HDT) bed rest and effect of lower body negative pressure in the first and the last week in humans. Twelve healthy male volunteers were exposed to -6 degrees HDT bed rest for 21 d. Six subjects received -30 mmHg LBNP sessions for 1 h per day from the 1st to the 7th day and from the 15th to the 21st day of the HDT, and six others served as control. Orthostatic tolerance was assessed by means of standard tilt test. Stroke volume (SV), cardiac output (CO), preejection period (PEP) and left ventricular ejection time (LVET) were measured before and during HDT. Before HDT, all the subjects in the two groups completed the tilt tests. After 10 d and 21 d of HDT, all the subjects of the control group and one subject of the LBNP group could not complete the tilt test due to presyncopal or syncopal symptoms. The mean upright time in the control group (15.0 +/- 3.2 min) was significantly shorter than those in the LBNP group (19.7 +/- 0.9 min). SV and CO decreased significantly in the control group on days 3 and 10 of HDT, but remained unchanged throughout HDT in the LBNP group. A significant increase in PEP/LVET was observed on days 3 and 14 of HDT in both groups. The PEP/LVET in the LBNP group was significantly lower on day 3 of HDT, while LVET in the LBNP group was significantly higher on days 3, 7 and 14 of HDT than those in the control group. The results of this study suggest that brief daily LBNP sessions used in the first and the last weeks of 21 d HDT bed rest were effective in diminished the effect of head-down tilt on orthostatic tolerance, and LBNP might partially improve cardiac pumping function and cardiac systole function.     

Effect of head-down tilt on respiratory responses and human inspiratory muscles activity

The effect of head-down tilt on respiration and diaphragmal and parasternal muscles activity was investigated in 11 healthy subjects. The short-time (30 min) head-down tilt posture (-30 degrees relatively horizont) increased the inspiratory time (P < 0.05), decreased breathing frequency (P < 0.05), inspiratory and expiratory flow rate (P < 0.05) and increased the airway resistance (P < 0.05) compared with values in vertical posture. There were no significant changes in tidal volume and minute ventilation. Constant values of tidal volume and minute ventilation during head-down tilt were provided by increasing in EMG activity of parasternal muscles more then twice. It was established that the contribution of chest wall inspiratory muscles increased while the diaphragm's contribution decreased during head-down spontaneous breathing. Maximal inspiratory effort (Muller's maneuver) during head-down tilt evoked the opposite EMG-activity pattern: the contribution of inspiratory thoracic muscles was decreased and diaphragm's EMG-activity was increased compared with vertical posture. These results suggest that coordinate modulations in inspiratory muscles activity allows to preserve the functional possibility of human inspiratory muscles during short-time head-down tilt.     

Monitoring immune system function and reactivation of latent viruses in the Artificial Gravity Pilot Study

Numerous studies have indicated that dysregulation of the immune system occurs during or after spaceflight. Using 21 day 6 head-down tilt bed rest as a spaceflight analog, this study describes the effects of a daily artificial gravity (AG) countermeasure treatment on immunity, stress, and reactivation of clinically important latent herpes viruses. Blood, saliva, and urine samples were collected from each of the 15 male test subjects (8 treatment, 7 control) periodically throughout the study. The immune assessment consisted of a comprehensive peripheral immunophenotype analysis, intracellular cytokine profiles, and measurement of T cell function. With the exception of mild reactivation of Epstein-Barr (EBV) and Varicella zoster (VZV) viruses, no significant changes in immune function were observed, suggesting that the AG countermeasure and the 21 day head-down tilt bed rest regimen had no adverse effect on immune function.     

Permanent depression of plasma cGMP during long-term space flight

The purpose of this study was to investigate plasma concentrations of cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP) during and after real and simulated space flight. Venous blood was obtained 3 min after the beginning and 2 min after the lower body negative pressure maneuver in two cosmonauts preflight (supine), inflight, and postflight (supine) and in five other subjects before, at the end, and 4 days after a 5-day head-down tilt (-6 degrees) bed rest. In cosmonaut 1 (10 days in space), plasma cGMP fell from preflight 4.3 to 1.4 nM on flight day 6, and was 3.0 nM on the fourth day after landing. In cosmonaut 2 (438 days in space), it fell from preflight 4.9 to 0.5 nM on on flight day 3, and stayed <0.1 nM with 5, 9, and 14 months in space, as well as on the fourth day after landing. Three months after the flight his plasma cGMP was back to normal (6.3 nM). Cosmonaut 2 also displayed relatively low inflight ANP values but returned to preflight level immediately after landing. In a ground-based simulation on five other persons, supine plasma cGMP was reduced by an average of 30% within 5 days of 6 degrees head-down tilt bed rest. The data consistently demonstrate lowered plasma cGMP with real and simulated weightlessness, and a complete disappearance of cGMP from plasma during, and shortly after long-duration space flight.     

Effect of head-down tilt on respiratory responses and human inspiratory muscle activity

The effect of a head-down tilt on the responses of the external respiration system and the functional capacity of the diaphragm and parasternal muscles were investigated in 11 healthy subjects. A 30-min head-down tilt posture (−30° relative to the horizontal) significantly increased the inspiratory time, decreased the respiration rate and the inspiratory and expiratory flow rates; and increased the airway resistance compared to these values in the vertical posture. There were no significant changes in tidal volume or minute ventilation. The electromyograms (EMGs) of the diaphragm and parasternal muscles showed that the constant values of tidal volume and minute ventilation during head-down tilt could be provided by an increase in the electric activity of the thoracic inspiratory muscles. It was established that the contribution of the thoracic inspiratory muscles increased, while the diaphragms’ contribution decreased, during patient, spontaneous breathing. The maximal inspiratory effort (Muller’s maneuver) during a head-down tilt evoked the opposite EMG-activity pattern: the contribution of inspiratory thoracic muscles was decreased and the diaphragm EMG activity was increased compared to the vertical posture. These results suggest that coordinated modulations in inspiratory muscle activity make it possible to preserve the functional reserve of human inspiratory muscles during a short-term head-down tilt.     

Determinants of atrial natriuretic factor secretion in dogs expanded with isotonic saline or colloid solutions.

Through increments in blood volume and atrial pressure are thought to be the primary stimuli for ANF secretion, plasma levels of this peptide do not always behave as a simple function of volume status. To outline the relationship between the latter and cardiac ANF release, we used five different volume-expansion protocols in anesthetized dogs. A stepwise expansion of plasma volume (PV) was achieved by two consecutive infusions: 0.9% saline followed or preceded by 4 or 25% bovine serum albumin (BSA), 4 or 25% dextran (Dx), or homologous plasma. Saline expansion led to a two- to four-fold increase in arterial plasma ANF level in all five protocols. Both 4 and 25% BSA caused no or very modest increase in plasma ANF, while all other colloid expanders caused the expected ANF release. In all protocols, plasma ANF closely correlated with central venous pressure (CVP). BSA expansion was the only protocol with no correlation between PV and ANF release. Changes in serum Ca2+ could not explain this finding. During BSA expansion, the lack of atrial response was related to the absence of increment (or even fall) in CVP despite the expanded PV. Similarly, urinary Na+ excretion was correlated both with CVP and ANF level but not with PV in BSA expansion. When the dogs were depleted of histamine before BSA infusion, the atrial secretory response was restored, suggesting that this colloid was associated with augmented capillary leakiness and vascular fluid efflux. These results show that the expansion of PV leads neither to ANF release nor to Na+ excretion if it is not accompanied by an expanded central blood volume with elevated atrial pressure.     

Effects of 9 weeks of hindlimb unloading on motor performances in adult rats

It has been reported that abnormal steps associated with an ankle hyper-extension during walking were observed in adult rats after 2 weeks of hindlimb suspension (Canu and Falempin, 1997 & 1998). But such phenomena were normalized after 7 days of reambulation recovery. Canu and Falempin (1996) suggested that the spinal cord has a capacity to generate a well-organized pattern of locomotion even after a period of muscle disuse. There are, however, no reports about the effects of more prolonged suspension on motor performances. In the present study, 7 weeks old male rats were hindlimb-unloaded by tail suspension for 9 consecutive weeks and landing performances in response to drop from head-down, head-up, or supine position were investigated during 8 weeks of recovery. Posture maintenance during right-left translation was also checked.     

Arterial baroreflex control of sympathetic vasoconstrictor traffic and orthostatic intolerance after head-down bed rest

The purpose of the present study is to examine the changes in the arterial baroreflex control of muscle sympathetic nerve activity (MSNA) after head-down bed rest (HDBR), in relation to orthostatic hypotension after HDBR. Therefore, we performed 60 degrees head-up tilt (HUT) tests before and after 14 days of HDBR, with monitoring MSNA, heart rate and blood pressure. We calculated the gain of the arterial baroreflex control of MSNA, and compared the gains between the subjects who did (defined as the fainters) and those who did not (defined as the nonfainters) become presyncopal in HUT tests after HDBR.     

Dynamic cerebral autoregulation is preserved during acute head-down tilt.

Complete ganglion blockade alters dynamic cerebral autoregulation, suggesting links between systemic autonomic traffic and regulation of cerebral blood flow velocity. We tested the hypothesis that acute head-down tilt, a physiological maneuver that decreases systemic sympathetic activity, would similarly disrupt normal dynamic cerebral autoregulation. We studied 10 healthy young subjects (5 men and 5 women; age 21 +/- 0.88 yr, height 169 +/- 3.1 cm, and weight 76 +/- 6.1 kg). ECG, beat-by-beat arterial pressure, respiratory rate, end-tidal CO2 concentration, and middle cerebral blood flow velocity were recorded continuously while subjects breathed to a metronome. We recorded data during 5-min periods and averaged responses from three Valsalva maneuvers with subjects in both the supine and -10 degrees head-down tilt positions (randomized). Controlled-breathing data were analyzed in the frequency domain with power spectral analysis. The magnitude of input-output relations were determined with cross-spectral techniques. Head-down tilt significantly reduced Valsalva phase IV systolic pressure overshoot from 36 +/- 4.0 (supine position) to 25 +/- 4.0 mmHg (head down) (P = 0.03). Systolic arterial pressure spectral power at the low frequency decreased from 5.7 +/- 1.6 (supine) to 4.4 +/- 1.6 mmHg2 (head down) (P = 0.02), and mean arterial pressure spectral power at the low frequency decreased from 3.3 +/- 0.79 (supine) to 2.0 +/- 0.38 mmHg2 (head down) (P = 0.05). Head-down tilt did not affect cerebral blood flow velocity or the transfer function magnitude and phase angle between arterial pressure and cerebral blood flow velocity. Our results show that in healthy humans, mild physiological manipulation of autonomic activity with acute head-down tilt has no effect on the ability of the cerebral vasculature to regulate flow velocity.