The OPG/RANKL/RANK system modulates calcification of common carotid artery in simulated microgravity rats by regulating NF-κB pathway.

Functional and structural adaptation of common carotid artery could be one of the important causes of postflight orthostatic intolerance after microgravity exposure, the mechanisms of which remain unclear. Recent evidence indicates that long-term spaceflight increases carotid artery stiffness, which might present a high risk to astronaut health and postflight working ability. Studies have suggested that vascular calcification is a common pathological change in cardiovascular diseases that is mainly manifested as an increase in vascular stiffness.

miR-137 and its target T-type Ca 3.1 channel modulate dedifferentiation and proliferation of cerebrovascular smooth muscle cells in simulated microgravity rats by regulating calcineurin/NFAT pathway.

Objectives: Postflight orthostatic intolerance has been regarded as a major adverse effect after microgravity exposure, in which cerebrovascular adaptation plays a critical role. Our previous finding suggested that dedifferentiation of vascular smooth muscle cells (VSMCs) might be one of the key contributors to cerebrovascular adaptation under simulated microgravity. This study was aimed to confirm this concept and elucidate the underlying mechanisms.

BMAL1 Disrupted Intrinsic Diurnal Oscillation in Rat Cerebrovascular Contractility of Simulated Microgravity Rats by Altering Circadian Regulation of miR-103/Ca1.2 Signal Pathway.

The functional and structural adaptations in cerebral arteries could be one of the fundamental causes in the occurrence of orthostatic intolerance after space flight. In addition, emerging studies have found that many cardiovascular functions exhibit circadian rhythm. Several lines of evidence suggest that space flight might increase an astronaut's cardiovascular risks by disrupting circadian rhythm.

Focal adhesions are involved in simulated-microgravity-induced basilar and femoral arterial remodelling in rats.

Recent studies have suggested that microgravity-induced arterial remodelling contributes to post-flight orthostatic intolerance and that multiple mechanisms are involved in arterial remodelling. However, the initial mechanism by which haemodynamic changes induce arterial remodelling is unknown. Focal adhesions (FAs) are dynamic protein complexes that have mechanotransduction properties.

Mechanics and composition of middle cerebral arteries from simulated microgravity rats with and without 1-h/d -Gx gravitation.

Background: To elucidate further from the biomechanical aspect whether microgravity-induced cerebral vascular mal-adaptation might be a contributing factor to postflight orthostatic intolerance and the underlying mechanism accounting for the potential effectiveness of intermittent artificial gravity (IAG) in preventing this adverse effect.

Methodology/principal Findings: Middle cerebral arteries (MCAs) were isolated from 28-day SUS (tail-suspended, head-down tilt rats to simulate microgravity effect), S+D (SUS plus 1-h/d -Gx gravitation by normal standing to simulate IAG), and CON (control) rats. Vascular myogenic reactivity and circumferential stress-strain and axial force-pressure relationships and overall stiffness were examined using pressure arteriography and calculated.

Mechanical properties and composition of mesenteric small arteries of simulated microgravity rats with and without daily -G(x) gravitation.

The aim of the present study was to evaluate the active and passive mechanical properties and wall collagen and elastin contents of mesenteric small arteries (MSAs) isolated from rats of 28-day simulated microgravity (SUS), countermeasure [S + D: SUS plus 1 h/d -G(x) to simulate intermittent artificial gravity (IAG)] and control (CON) groups. Three mechanical parameters were calculated: the overall stiffness (β), circumferential stress (σ(θ))-strain (ε(θ)) relationship and pressure-dependent incremental elastic modulus (E(inc,p)). Vessel wall collagen and elastin percentage were quantified by electron microscopy.

[In-vivo and ex-vivo studies on region-specific remodeling of large elastic arteries due to simulated weightlessness and its prevention by gravity-based countermeasure].

The present study was designed to test the hypothesis that a medium-term simulated microgravity can induce region-specific remodeling in large elastic arteries with their innermost smooth muscle (SM) layers being most profoundly affected. The second purpose was to examine whether these changes can be prevented by a simulated intermittent artificial gravity (IAG). The third purpose was to elucidate whether vascular local renin-angiotensin system (L-RAS) plays an important role in the regional vascular remodeling and its prevention by the gravity-based countermeasure.

[Effects and mechanism of low frequency stimulation of pedunculopontine nucleus on spontaneous discharges of ventrolateral thalamic nucleus in rats].

Parkinson's disease is a progressive neurodegenerative disorder characterized clinically by rigidity, akinesia, resting tremor and postural instability. It has recently been suggested that low frequency stimulation of the pedunculopontine nucleus (PPN) has a role in the therapy for Parkinsonism, particularly in gait disorder and postural instability. However, there is limited information about the mechanism of low frequency stimulation of the PPN on Parkinson's disease.

Activation of BKCa channel is associated with increased apoptosis of cerebrovascular smooth muscle cells in simulated microgravity rats.

Cerebral arterial remodeling is one of the critical factors in the occurrence of postspaceflight orthostatic intolerance. We hypothesize that large-conductance calcium-activated K(+) (BK(Ca)) channels in vascular smooth muscle cells (VSMCs) may play an important role in regulating cerebrovascular adaptation during microgravity exposure. The aim of this work was to investigate whether activation of BK(Ca) channels is involved in regulation of apoptotic remodeling of cerebral arteries in simulated microgravity rats.

Activation of cloned BK(Ca) channels in nitric oxide-induced apoptosis of HEK293 cells.

The large conductance Ca(2+)-activated K(+) (BK(Ca)) channels are highly expressed in vascular smooth muscle cells (VSMCs) and play an essential role in the regulation of various physiological functions. Besides its electrophysiological function in vascular relaxation, BK(Ca) has also been reported to be implicated in nitric oxide (NO)-induced apoptosis of VSMCs. However, the molecular mechanism is not clear and has not been determined on cloned channels.

[Comparison of biomechanical behavior of cerebral and mesenteric small arteries of simulated microgravity rats].

The aim of the present study was to further elucidate the mechanisms of vascular adaptation to microgravity and its gravity-based countermeasure by a biomechanical approach. Active (the dissected vessel segment was superfused with PPS) and passive (while it was superfused with Ca(2+)-free PPS) biomechanical properties of mesenteric third-order small arteries and middle cerebral arteries isolated from 3-day simulated microgravity (SUS), countermeasure (STD, daily 1 h of -G(x) gravitation), and control (CON) groups of rats were studied. The following mechanical parameters were calculated: the overall stiffness parameter of passive vessels (beta), circumferential stress (sigma(theta))-strain (epsilon(theta)) relationship, and pressure-dependent incremental elastic modulus (E(inc,p)) of both active and passive vessels, and vascular smooth muscle (VSM) activity-dependent incremental modulus (E(inc,a)).

Investigation of mass transfer in the ion-exchange-membrane-partitioned free-flow IEF system for protein separation.

In this study, novel polysulfone-based cation-exchange membranes with strong mechanical strength have been developed and applied in ion-exchange-membrane-partitioned free-flow IEF (IEM-FFIEF) to replace the conventional immobiline membranes. A fundamental understanding of protein mass transfer in the IEM-FFIEF process has been revealed experimentally with the aid of membrane-based boundary effect model contributed by Ennis et al. we have proven experimentally the existence of a pH gradient across the membrane cross-section when an IEM-FFIEF system is in operation.

Coexpression and characterization of the human large-conductance Ca(2+)-activated K (+) channel alpha + beta1 subunits in HEK293 cells.

Large-conductance Ca(2+)-activated K(+) channel is formed by a tetramer of the pore-forming alpha-subunit and distinct accessory beta-subunits (beta1-beta4) which contribute to BK(Ca) channel molecular diversity. Accumulative evidences indicate that not only alpha-subunit alone but also the alpha + beta subunit complex and/or beta-subunit might play an important role in modulating various physiological functions in most mammalian cells. To evaluate the detailed pharmacological and biophysical properties of alpha + beta1 subunit complex or beta1-subunit in BK(Ca) channel, we established an expression system that reliably coexpress hSloalpha + beta1 subunit complex in HEK293 cells.

Blockade of AT1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats.

Previous studies have demonstrated activation of the local renin-angiotensin system in hindlimb unweighting (HU) rat vasculature. The present study intended to identify the effects of blockade of angiotensin II (ANG II) type 1 (AT(1)) receptors with losartan on vascular reactivity, nitric oxide synthase (NOS) expression, and superoxide anion (O(2)(*-)) levels in 3-wk HU rat cerebral and carotid arteries. Three weeks later, vasoconstriction, vasodilatation, endothelial NOS (eNOS) and inducible NOS (iNOS) protein, as well as O(2)(*-) levels in rat cerebral and carotid arteries were examined.

Cardiovascular changes of conscious rats after simulated microgravity with and without daily -Gx gravitation.

This study was designed to test the hypothesis that postsuspension cardiovascular manifestation in conscious rats after a medium-term (28-day) tail suspension (SUS) is hypertensive and tachycardiac and can be prevented by a countermeasure of daily 1-h dorsoventral (-G(x)) gravitation provided by standing (STD). To assess associated changes in cardiovascular regulation, blood pressure (BP) and heart rate (HR) variability were analyzed by spectral analysis computed by parametric autoregressive (AR) method and by nonlinear recurrence quantification analysis (RQA) and approximate entropy (ApEn) measure. The results showed that conscious SUS rats manifested hypertensive and tachycardiac response before and after being released from suspension compared with the controls, and the countermeasure of 1 h/day -G(x) prevented the hypertensive response.

[Spectral analysis of blood pressure signal in conscious rats released from simulated microgravity].

The aim of the present study was to examine whether there are changes in systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) and their spectral indices in conscious free-moving rats after tail-suspension for 28 d. The tail-suspended hindlimb-unloaded (HU) rat model was used to simulate the cardiovascular effect of microgravity and the post-spaceflight cardiovascular dysfunction. The auto- and cross-spectral analysis of SBP variability (SBPV) and HR variability (HRV) were performed by the method based on the autoregressive model (AR), and the auto-spectral results was compared with the results from the classical periodogram method.

Effectiveness of daily short-duration standing in preventing post-suspension cardiovascular dysfunction in rats assessed by cardiovascular signal analysis.

The aim of the present study was to clarify whether simulated microgravity-induced post-suspension cardiovascular deconditioning in rats could be prevented by daily short-duration standing (STD). Three groups of rats were used as subjects to perform the experiments. Compared to a control group of male Sprague-Dawley rats (CON), a group of rats with tail-suspension (SUS) for 28 d was used to simulate cardiovascular deconditioning due to microgravity.

[Effects of simulated microgravity on L-ARG-NO-CGMP pathway of abdominal aorta in rats].

Aim: To investigate the effects of simulated microgravity on dilatory responsiveness and NOS expression of abdominal aorta in rats.

Methods: Twenty male healthy SD rats, which body weight ranged from 300 g to 330 g, were divided into control group and simulated microgravity group randomly. After 4 weeks, using isolated arterial rings from rats, arterial dilatory responsiveness of abdominal aorta were examined in vitro.

Daily 4-h head-up tilt is effective in preventing muscle but not bone atrophy due to simulated microgravity.

To assess the potential value of intermittent artificial gravity as an efficient countermeasure, our previous studies have showed that daily 4-h standing (STD) is sufficient in counteracting muscle atrophy but not bone atrophy induced by simulated microgravity. The aim of the present study was to determine whether intermittent gravitational loading by daily 2-h or 4-h, +45 degrees head-up tilt (HUT) is more effective than STD in counteracting muscle and, particularly, bone atrophy due to simulated microgravity. Sprague-Dawley male rats weighing 290-300 g were subjected to a 28-d tail-suspension to simulate microgravity deconditioning.

[The inhibiting effect of niflumic acid on airway hyperresponsiveness in asthmatic mice].

Objective: To evaluate the inhibiting effect of niflumic acid (NFA), an inhibitor of calcium-activated chloride channel (ClCa) on airway epithelium, on the airway hyperresponsiveness in asthmatic mice.

Methods: BALB/c mice were randomly divided into an asthma group (A group), a NFA prevention asthmatic group (B group) and a sham-challenged group (C group). The airway pressure time index (APTI) and the content of ET-1 and NO in bronchoalveolar lavage fluid (BALF) in all groups were measured.

Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity.

This study was designed to compare the effectiveness of daily short-duration -Gx gravity exposure in preventing adverse changes in skeletal and cardiac muscles and bone due to simulated microgravity. Tail suspension for 28 days was used to simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G for 1, 2, or 4 h/day or centrifugation (CEN) at 1.

[Decrease in tetanic tension in 4-week tail-suspended rat soleus and analysis of its underlying mechanisms].

Objective. To observe the dynamic changes in tetanic tension in 4-week tail-suspended rat soleus (SOL) and extensor digitorum longus muscle (EDL) and to elucidate its underlying mechanisms. Method.