TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively.

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.

Berberine reduced blood pressure and improved vasodilation in diabetic rats.

Hyperglycemia and hypertension are considered to be the two leading risk factors for vascular disease in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and hypertension at the same time in diabetes. The objectives of this study are to investigate whether berberine treatment could directly reduce blood pressure and identify the molecular mechanism underlying the vascular protection of berberine in diabetic rats.

Salidroside contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic Goto-Kakizaki Rats by inhibition of L-type calcium channel in smooth muscle cells.

Background: Vascular disease is a common and often severe complication in diabetes mellitus. Hyperglycemia and hypertension are considered to be two of the leading risk factors for vascular complications in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and blood pressure in diabetic patients at the same time.

Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca²⁺ handling in smooth muscle cells.

Background: Vascular dysfunction is a distinctive phenotype in diabetes mellitus. Current treatments mostly focus on the tight glycemic control and few of these treatments have been designed to directly recover the vascular dysfunction in diabetes. As a classical natural medicine, berberine has been explored as a possible therapy for DM.

28-Day hindlimb unweighting reduces expression of Rho kinase and inhibits its effects in femoral artery of rat.

Previous studies have demonstrated inconsistent roles of Rho kinase (ROCK) in the decreased vasoconstriction of rat hindquarter vessels induced by hindlimb unweighting (HU). The present study was designed to determine the unclear role of ROCK in the mediation of HU-induced decreased femoral arterial vasoconstriction. 28-day HU rat was adopted as the animal model.

Simulated microgravity promotes monocyte adhesion to rat aortic endothelium via nuclear factor-κB activation.

Microgravity-induced vascular remodelling may play an important role in post-spaceflight orthostatic intolerance. In this study, we aimed to investigate the effects of simulated microgravity on monocyte adhesion to aortic endothelium in hindlimb unweighted rats and to elucidate the underlying mechanisms associated with this event. Sprague-Dawley rats were subjected to 4-week hindlimb unweighting to simulate microgravity.

Simulated microgravity induces an inflammatory response in the common carotid artery of rats.

Post-spaceflight orthostatic intolerance is one of the most important adverse effects after exposure to space microgravity, and there are still no effective countermeasures. It has been considered that arterial remodeling may play an important role in the occurrence of post-spaceflight orthostatic intolerance, but the cellular mechanisms remain unknown. In this study, we investigated whether an inflammatory response exists in the common carotid artery of rats exposed to simulated microgravity.

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.

Lysosome-membrane fusion mediated superoxide production in hyperglycaemia-induced endothelial dysfunction.

Lysosomal exocytosis and fusion to cellular membrane is critical in the oxidative stress formation of endothelium under apoptotic stimulus. We investigated the role therein of it in hyperglycaemia-induced endothelial dysfunction. The lysosome-membrane fusion was shown by the expression of lamp1, the lysosomal membrane marker, on cellular membrane and the transportation of lysosomal symbolic enzymes into cultural medium.

NAD(P)H oxidase inhibiting with apocynin improved vascular reactivity in tail-suspended hindlimb unweighting rat.

Recent studies suggested that reactive oxygen species derived from nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase is of functional importance in modulating vascular tone, and we have previously detected excessive superoxide production in tail-suspended hindlimb unweighting (HU) rat cerebral and carotid arteries. HU rat was a widely used model to simulate physiological effects on the vasculature. The present study tended to investigate whether NAD(P)H oxidase inhibition with apocynin influences vasoconstriction, endothelium-dependent relaxation, and nitrite/nitrate (NOx) content in HU rat cerebral and carotid arteries.

[Short-term simulated weightlessness enhances response of L-type calcium channel to angiotensin II in cerebral vascular smooth muscle cells in rats].

Some studies suggest that the calcium channels and rennin-angiotensin system (RAS) play pivotal roles in the region-specific vascular adaptation due to simulated weightlessness. This study was designed to clarify if angiotensin II (Ang II) was involved in the adaptational change of the L-type calcium channel (Ca(L)) in the cerebral arterial vascular smooth muscle cells (VSMCs) under simulated weightlessness. Tail suspension (SUS) for 3 d was used to simulate immediate early cardiovascular changes to weightlessness.

Differential vascular cell adhesion molecule-1 expression and superoxide production in simulated microgravity rat vasculature.

Exposure to microgravity leads to orthostatic intolerance in astronauts and differential vascular structural and functional adaptations have been implicated in its occurrence. The present study tended to clarify the characteristics of vascular inflammation and oxidative stress in hindlimb unweighting (HU) rat vasculature. Male Sprague-Dawley rats were randomly divided into control (CON) and hindlimb unweighting (HU) groups.

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.

Contrasting effects of simulated microgravity with and without daily -Gx gravitation on structure and function of cerebral and mesenteric small arteries in rats.

This study was designed to test the hypothesis that a 28-day tail suspension (SUS) could induce hypertrophy and enhanced myogenic and vasoconstrictor reactivity in middle cerebral arteries (MCAs), whereas atrophy and decreased myogenic and vasoconstrictor responses in mesenteric third-order arterioles (MSAs). Also, in addition to the functional enhancement in MCAs, structural changes in both kinds of arteries and functional decrement in MSAs could all be prevented by the intervention of daily 1-h dorsoventral (-G(x)) gravitation by restoring to standing posture. To test this hypothesis, vessel diameters to pressure alterations and nonreceptor- and receptor-mediated agonists were determined using a pressure arteriograph with a procedure to measure in vivo length and decrease hysteresis of vessel segments and longitudinal middlemost sections of vessels fixed at maximally dilated state were examined using electron microscopy and histomorphometry.

[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)).

[Differential effect of simulated microgravity on myogenic tone of middle cerebral and mesenteric small arteries in rats].

The aim of the present study was to investigate the effect of a short-term (3-day) simulated microgravity with and without daily dorsoventral gravitation (-G(x)) for 1 h on myogenic tone and vasoconstrictor responsiveness of the middle cerebral artery and mesenteric third-order small artery in rats. The tail-suspension (SUS) model was used to simulate cardiovascular deconditioning due to microgravity. Daily restoring to normal standing (STD) posture for 1 h was adopted to provide -G(x) as the countermeasure.

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.