Weightlessness simulations for cardiovascular and muscle systems: validity of rat models.

Animal models are widely used to evoke responses comparable to those obtained during weightlessness. Two models are reviewed; one examines cardiovascular responses and cephalad fluid shifts in head down tilting (HDT), and the other examines atrophy in load bearing muscles by unloading the hind limbs. Cephalad fluid shifts result in diuresis, natriuresis, and kaliuresis.

Biochemical characteristics of beta-adrenoceptors in rats after an 18-day spaceflight (LMS-STS78).

Background: To ascertain whether there was autonomic adaptation with the development of adrenoceptor hypersensitivity under microgravity, the biochemical properties of the beta-adrenoceptors were determined using (125I)iodocyanopindolol (ICYP) binding in rats flown for 18 d onboard the space shuttle.

Methods: This study was performed on heart and kidneys of 3 groups of 12 animals: the flight and 2 ground control (vivarium and AEM) groups. To distinguish the possible role of the corticosteroids, half of each animal group was bilaterally adrenalectomized (ADX rats) with an aldosterone and corticosterone supplementation while the other half was SHAM operated.

Effect of a 14-day hindlimb suspension on beta-adrenoreceptors in rats.

Exposure to long-term simulated microgravity exhibits reduced sympathetic nervous system activity. This study tested the hypothesis that the hypersensitivity of adrenoreceptors would explain partly many other features of the hemodynamic consequences of return from space. The biochemical properties of the beta adrenoreceptors (betaAR) were determined using 125I-cyanopindolol (125I-CYP) binding in three rat groups: (1) The first experimental group consisted of 24 h-restrained orthostatic rats in the horizontal position, to test the early effect of the attachment to the suspension device; (2) the second experimental group consisted of 24 h-restrained antiorthostatic rats, to test the early effect of the suspension; (3) the third experimental group consisted of 14 day-restrained antiorthostatic rats, to test the long term effect of the suspension.

Cardiac atrial natriuretic peptide (ANP) in rat dams and fetuses developed in space (NIH-R1 and NIH-R2 experiments).

NIH-R1 and R2 missions, conducted by NASA, allowed us to study the effects of the microgravitational environment 1) on cardiac ANP in pregnant rats, spaceflown for 11 days and dissected after a 2-day readaptation to Earth's gravity, after natural delivery, and 2) on maturation of cardiac ANP system in rat fetuses developed for 11 days in space and dissected on the day of landing, 2 days before birth. Immunocytochemical and electron microscopy analyses showed a typical formation of ANP-containing granules in atrial myocytes, in both dams and fetuses. Using competitive RT-PCR and radioimmunoassays, we observed that, after 2 days of readaptation to Earth's gravity, cardiac ANP biosynthesis of rat dams flown in space was increased by about twice, when compared to Synchronous and Vivarium Control rats.

Regional blood flow in conscious rats after head-down suspension.

Exposure to microgravity in humans causes cardiovascular deconditioning affecting blood pressure, heart rate and vascular responsiveness. This study investigated cardiac output, arterial blood pressure and regional blood flows [radioactive microspheres: 57Co, 15.5 (SEM 0.

Recording heart rate and blood pressure in rats during parabolic flight.

The way in which the cardiovascular system adapts to weightlessness is still under discussion. No data are yet available on the responses of rats during space flight, although this animal is commonly used in simulation studies. We have designed and tested a protocol to study the short term responses of the cardiovascular system to weightlessness during parabolic flight.

Cardiovascular adaptations to parabolic flight in rats: a radio-telemetry feasibility study.

This experiment was a feasibility study which consisted in investigating arterial blood pressure and heart rate to transient and repeated exposure to microgravity in eight unrestrained rats previously implanted with radio-telemetry transmitter. The aim was to perform such recordings throughout all the phases of a parabola during parabolic flights. This study revealed that it was possible to collect the radio-signal without any interference with electronic or magnetic environment.

Restraint vs. hindlimb suspension on fluid and electrolyte balance in rats.

To determine the effect of hindlimb suspension on body fluid volume, salt and water balance, and relevant hormones, two series of experiments were performed in an experimental protocol including periods of isolation (7 days), horizontal attachment (7 days), and suspension (14 days). 1) During the first experiment, water and electrolyte balance, arginine vasopressin (AVP), and guanosine 3',5'- cyclic monophosphate (cGMP) were determined in urine, atrial natriuretic peptide in plasma and atria, and renin concentration and AVP in plasma in 30 rats. 2) During the second experiment, blood volume and extracellular fluid volume were measured by a dilution technique (Evans blue and sodium thiocyanate) in another 30 rats.

Central and peripheral noradrenergic responses to 14 days of spaceflight (SLS-2) or hindlimb suspension in rats.

Introduction: The purposes of this work were to assess the influence of microgravity on the central and peripheral noradrenergic activity to reevaluate SLS-1 mission findings and to compare it with that of simulated microgravity in rats.

Methods: The norepinephrine (NE) contents of the brainstem cell groups (A1, A2, A5, and A6) and organs (heart and kidneys) involved in blood pressure regulation were determined in rats after a 14-d spaceflight (SLS-2 with animals sacrificed 6 h after landing) and after a 14-d hindlimb suspension followed with 6 h of recovery.

Results: After SLS-2 spaceflight, NE contents were not significantly different between flight and ground-based rats either in A1 (5.

Cortico-adrenal function under simulated weightlessness during gestation in the rat--effects on fetal development.

To examine the effects of simulated weightlessness on cortico-adrenal function and on fetal development, we suspended pregnant rats for 20 days. The levels of adrenal and plasma corticosterone were examined in mothers and in fetuses. The animal control group was kept single in standard cages.

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.

Central and peripheral sympathetic activities in rats during recovery from simulated weightlessness.

Rats were tail suspended, keeping their forelimbs weight bearing for 14 days, and then allowed to recover for a short (6-h) or a long (24-h) period to assess the behavior of the sympathetic nervous system after weightless simulation. Sympathetic activity was determined by measuring norepinephrine (NE) turnover in the brain stem cell groups involved in central blood pressure control and in organs playing a key role in the cardiovascular regulation (heart and kidneys). The NE turnover was greatly reduced in the rostral (-56%; P < 0.

Choroidal responses in microgravity. (SLS-1, SLS-2 and hindlimb-suspension experiments).

Fluid and electrolyte shifts occurring during human spaceflight have been reported and investigated at the level of blood, cardiovascular and renal responses. Very few data were available concerning the cerebral fluid and electrolyte adaptation to microgravity, even in animal models. It is the reason why we developed several studies focused on the effects of spaceflight (SLS-1 and SLS-2 programs, carried on NASA STS 40 and 56 missions, which were 9- and 14-day flights, respectively), on structural and functional features of choroid plexuses, organs which secrete 70-90% of cerebrospinal fluid (CSF) and which are involved in brain homeostasis.

[Involvement of urodilatin in the hydro-electrolytic modifications induced in man by a 6 degree head-down tilt].

On 6 healthy men, we measured: 1/ the effects of 28-day -6 degrees head-down tilt on the excretion of urodilatin and 2/ the relationship between urodilatin and urinary fluid, or sodium excretion. Aliquots of the pooled 24-h urine output were used. Urodilatin increased parallel to urinary fluid or Na+ at first day of head-down tilt.

Cardiovascular variability and baroreceptor reflex sensitivity over a 14-day tail suspension in rats.

To verify whether a long-term weightlessness simulation was associated with development of cardiovascular deconditioning, male Wistar rats were tail suspended for 13 days and then removed for a 24-h recovery. Blood pressure (BP) and heart rate (HR) responses, their spectral properties, and the pharmacologically tested baroreceptor reflex sensitivity were studied throughout the suspension period and after removal from the tail suspension device. BP, HR, and their variability were not altered over the experimental period, and there were no indications of orthostatic intolerance on release from head-down suspension.

Comparison of the effects of spaceflight and hindlimb-suspension on rat pituitary vasopressin and brainstem norepinephrine content.

To compare actual spaceflight to ground-based simulation (hindlimb-suspension), we measured the norepinephrine (NE) content in A1, A2, A5 and A6 (locus coeruleus) and the vasopressin content in the neurohypophysial system. The experimental period was of 9 days' duration. The NE content in the locus coeruleus decreased significantly in rats flown for 9 days (67%, p < 0.

Sympathetic nervous activity and cardiovascular variability after a 3-day tail suspension in rats.

The effects of a 3-day tail suspension on central and peripheral sympathetic activity were studied in rats by determining the in vivo noradrenaline (NA) turnover in the brain cell groups involved in central blood pressure control (A1, A2, A5 and A6) and in two peripheral organs, heart and kidneys. In addition, cardiovascular parameters and their variabilities were investigated by recording blood pressure (BP) and heart rate (HR) before and after suspension. These measurements were processed by spectrum analysis to assess the influence of tail suspension on autonomic balance.

Central and peripheral norepinephrine turnover after hindlimb suspension in the rat.

After a 9-d hindlimb suspension, the turnover rate of norepinephrine (NE) in rats was determined in A1, A2 (rostral and caudal), A5 and A6 cell groups, as well as in peripheral target organs (heart and kidneys). The NE turnover rate decreased after hindlimb suspension respectively in caudal A2 (67.5%, p < 0.

Effects of a short term hindlimb suspension on central and peripheral norepinephrine turnover in rats.

The loss of appropriate cardiovascular reflexes which contributes to the cardiovascular deconditioning observed after an exposure to actual or simulated microgravity (in man or animals) is well known, but the mechanisms responsible remain unclear. This protocol, a 2.5 h hindlimb suspension in rats, was undertaken to study the early adaptation of the sympathetic neurons involved in arterial pressure regulation: we determined central norepinephrine (NE) turnover in the brainstem catecholaminergic cell groups responsible for the central cardiovascular regulation i.