This study was designed to clarify whether simulated microgravity can induce differential changes in the current and protein expression of the L-type Ca(2+) channel (Ca(L)) in cerebral and mesenteric arteries and whether these changes can be prevented by daily short-duration -G(x) exposure. Tail suspension [hindlimb unloading (HU)] for 3 and 28 days was used to simulate short- and medium-term microgravity-induced deconditioning effects. Standing (STD) for 1 h/day was used to provide -G(x) as a countermeasure. Whole cell patch-clamp experiments revealed an increase in current density of Ca(L) of vascular smooth muscle cells (VSMCs) isolated from cerebral arteries of rats subjected to HU and a decrease in VSMCs from mesenteric arteries. Western blot analysis revealed a significant increase and decrease of Ca(L) channel protein expression in cerebral and small mesenteric arterial VSMCs, respectively, only after 28 days of HU. STD for 1 h/day did not prevent the increase of Ca(L) current density in cerebral arterial VSMCs, but it prevented completely (within 3 days) and partially (28 days) the decrease of Ca(L) current density in small mesenteric arterial VSMCs. Consistent with the changes in Ca(L) current, STD for 1 h/day did not prevent the increase of Ca(L) expression in cerebrovascular myocytes but did prevent the reduction of Ca(L) expression in mesenteric arterial VSMCs subjected to 28 days of HU. These data indicate that simulated microgravity up- and downregulates the current and expression of Ca(L) in cerebral and hindquarter VSMCs, respectively. STD for 1 h/day differentially counteracted the changes of Ca(L) function and expression in cerebral and hindquarter arterial VSMCs of HU rats, suggesting the complexity of the underlying mechanisms in the effectiveness of intermittent artificial gravity for prevention of postflight cardiovascular deconditioning, which needs further clarification.

BackgroundThe differential adaptations of cerebrovasculature and small mesenteric arteries could be one of critical factors in postspaceflight orthostatic intolerance, but the cellular mechanisms remain unknown. We hypothesize that there is a differential regulation of intracellular Ca2+ determined by the alterations in the functions of plasma membrane CaL channels and ryanodine-sensitive Ca2+ releases from sarcoplasmic reticulum (SR) in cerebral and small mesenteric vascular smooth muscle cells (VSMCs) of simulated microgravity rats, respectively.Methodology/Principal FindingsSprague-Dawley rats were subjected to 28-day hindlimb unweighting to simulate microgravity. In addition, tail-suspended rats were submitted to a recovery period of 3 or 7 days after removal of suspension. The function of CaL channels was evaluated by patch clamp and Western blotting. The function of ryanodine-sensitive Ca2+ releases in response to caffeine were assessed by a laser confocal microscope. Our results indicated that simulated microgravity increased the functions of CaL channels and ryanodine-sensitive Ca2+ releases in cerebral VSMCs, whereas, simulated microgravity decreased the functions of CaL channels and ryanodine-sensitive Ca2+ releases in small mesenteric VSMCs. In addition, 3- or 7-day recovery after removal of suspension could restore the functions of CaL channels and ryanodine-sensitive Ca2+ releases to their control levels in cerebral and small mesenteric VSMCs, respectively.ConclusionsThe differential regulation of CaL channels and ryanodine-sensitive Ca2+ releases in cerebral and small mesenteric VSMCs may be responsible for the differential regulation of intracellular Ca2+, which leads to the altered autoregulation of cerebral vasculature and the inability to adequately elevate peripheral vascular resistance in postspaceflight orthostatic intolerance.

This study was designed to test the hypothesis that a medium-term simulated microgravity by tailsuspension (SUS) induces hypertrophic and atrophic changes in the common carotid artery and abdominal aorta with their innermost smooth muscle (SM) layers being most profoundly affected. The second purpose was to elucidate whether vascular local renin-angiotensin system (L-RAS) plays an important role in the differential remodeling of the two kinds of large arteries by examining the gene and protein expression of angiotensinogen (A O) and angiotensin II receptor type 1 (AT1R) and their localization in the vessel wall. The results showed that SUS induced an increase in the media thickness of the common carotid artery due to hypertrophy of the four SM layers and a decrease in the total crosssectional area of the nine SM layers of the abdominal aorta without significant change in its media thickness. Irrespective of the nature of remodeling, the most prominent changes were in the innermost layers. Immunohistochemistry, in situ hybridization, Western blot, and real time quantitative PCR analysis revealed that SUS induced an up-and down-regulation in A O and AT1R expression in the common carotid artery and abdominal aorta, respectively. In conclusion, our findings have demonstrated some special features in the structural adaptation of large elastic arteries due to a mediumterm simulated microgravity.

Our aim was to investigate the effects of acute cold pressor test (CPT) on augmentation index (AI) and wave intensity (WI) indexes from right common carotid artery (RCCA) and right common femoral artery (RCFA) and to test whether the reflection coefficient (RC) from wave intensity analysis can reflect the distal vascular resistance (DVR) accurately. Forty-three healthy males were randomly selected for measurements at baseline and 1 min after CPT at RCCA or RCFA. CPT induced similar increases of heart rate and blood pressure in RCCA and RCFA groups with their pulse pressures unchanged. The W(2) (the second peak of WI) was too obscure in RCFA to be analyzed. The W(1) (the first peak of WI) of both arteries, W(1)-W(2) (interval between W(1) and W(2)), and NA (negative area between W(1) and W(2), indicating reflected waves) of RCCA and the R-W(1) (interval between the R wave of ECG and W(1)) of RCFA decreased obviously, whereas the W(2) and R-W(1) of RCCA and the RC (calculated as NA/W(1)) of RCFA increased with no changes in the RC of RCCA and the NA of RCFA during CPT compared with baseline. The AIs from both arteries increased significantly after CPT. These results suggested that acute CPT has opposing effects on cerebral and peripheral vascular resistances, with the former decreased and the latter increased. The RCs from RCCA and RCFA are more associated with the changes of cerebral and peripheral vascular resistances, respectively, than the NA and AI, and the RC is of guiding value in assessing DVR.

Background: Oxidative stress (OS) is an essential factor in the pathogenesis of branch retinal vein occlusion (BRVO). Studies have demonstrated the role of hydrogen gas in the regulation of OS. This study was designed to evaluate the effecacy of hydrogen gas on the BRVO rat model. Methods: Twenty-four BRVO rats were randomly divided into two groups: the hydrogen gas (H) group (42% H2, 21% O2, 37% N2) and the model (M) group (21% O2, 79% N2). Rats in the H group inhaled hydrogen gas for 8 h every day up to 30 d post-occlusion. Twelve age-matched healthy rats served as the control (C) group. Retinal function and morphology were detected at 1, 7, 14 and 30 d post-occlusion. Furthermore, the expression of vascular endothelial growth factor (VEGF-α) was detected by immunofluorescent staining. Results: Full-field electroretinography (ffERG) revealed that the amplitude of the b-wave (dark-adaptation 3.0 response), the amplitude of the OPs2 wave and the light-adapted flicker response in the H group were all higher than those in the M group at 7 d post-occlusion (all p<0.05). The reopen time of occlusive retinal vessels in the H group was 2.235 ± 1.128 d, which was shorter than that in the M group (4.234±2.236 d, p<0.05). The rats in the H group had a thinner IPL+GCL+NFL and an increased total retina compared with those in the M group at 3 d post-occlusion (p<0.05), while the rats in the H group had a thicker INL, IPL+GCL+NFL and total retina compared with those at 7, 14 and 30 d post-occlusion (p<0.05). Moreover, the flow velocity of ear vein blood was increased in the H group compared with that in the M group (p<0.05). The expression of VEGF-α in the H group was dramatically decreased compared with that in the M group at 1, 7 and 14 d post-occlusion (p<0.05), while the expression kept in similar level at 30 d post-occlusion (p>0.05). Conclusions: Our findings demonstrate that inhalation of hydrogen gas could alleviate retinal oedema, shorten reopen time and improve retinal function, and the potential mechanism might be related to a decrease in VEGF-α expression.