| Humans exposed to microgravity often exhibit signs of cardiovascular deconditioning marked by orthostatic intolerance and reduced exercise capacity on reexposure to gravity. The impaired cardiovascular response to standing after return from space might be among the highest risks to the safety, well-being, and performance of astronauts. In addition to hypovolemia, postflight cardiovascular deconditioning has also been associated with diminished cardiac and vascular function. All gravitational blood pressure gradients will disappear during microgravity exposure. Thus, a redistribution of transmural pressures and flows across and within the arterial vasculature is induced by the removal of gravity. Therefore, in humans, blood vessels in dependent body regions are chronically exposed to lower than normal upright 1-G blood pressure, whereas vessels in upper body regions are exposed to higher than normal 1-G blood pressure. Our previous ground-based animal studies have shown for the first time that simulated microgravity may induce upward and downward regulations in function, structure, and innervation state of the medium- and small-sized muscular arteries from fore (cerebral) and hind body parts of the same animal subjected to tail-suspended head-down tilt (SUS). On the basis of these findings and the relevant ground-based and spaceflight studies reported recently, we have raised the"peripheral effector mechanism hypothesis". We suggested that, in addition to hypovolemia, the microgravity-induced adaptation changes in function and structure of cardiac muscle and vascular smooth muscle might be another important factor responsible for postflight cardiovascular dysfunction. Our previous studies have also shown that the ion channel remodeling mechanism of vascular smooth muscle cells (VSMCs) and vascular local renin-angiotensin system (L-RAS) might be involved in vascular region-specific adaptational changes to microgravity. Furthermore, currently used, exercise-based countermeasures seem insufficient to prevent the occurrence of cardiovascular dysfunction in future long-duration, exploration class mission. In the past two decades, intermittent artificial gravity (IAG) by incorporating a short-arm centrifuge into the spacecraft has been suggested as a gravity-based countermeasure for future spaceflight. Our previous studies have shown that daily short-duration exposure to -Gx (dorsoventral) gravitation by standing (STD) to restore the rat's orthostatic posture , or -Gx with +Gz component by +45°head-up tilt, which mimics the IAG countermeasure, is surprisingly effective in preventing myocardial contractility depression and vascular changes. For example, it has been demonstrated that daily 1-h -Gx by STD is sufficient to prevent the differential changes in two kinds of medium-sized conduit arteries that might occur due to a 28-d simulated microgravity alone. Our work has further shown that simulated microgravity increases and decreases current densities and protein expression of CaL in cerebral and mesenteric arterial VSMCs,the countermeasure of 1 h/d -Gx can prevents the change of mesenteric artery but cannot prevent the change in cerebral artery. This study is on the basis of such hypothesis that in middle cerebral artery, 1h/d -Gx can prevent the thickening of structure induced by microgravity, but can not prevent the increase of myogenic tone and the enhancement of vasoconstriction. In mesenteric small artery, not only the 1h/d -Gx can prevent the attentuation of vasoconstriction and thinningz of structure induced by microgravity, but also can prevent the increase of myogenic tone.To confirm our hypothesis mentioned above, we use tail-suspension rat model to simulate the cardiovascular dysfunction after flight and daily 1-h standing to simulate the countermeasure effect of IAG. The changes of vessel function and structure in rats were examined. The main work was divided into two parts:(1) The first part of work was aim to examine the change of myogenic tone, the vasoconstriction of middle cerebral artery and mesenteric small artery after a short-term (3-day) simulated microgravity with and without 1-h/d -Gx countermeasure. After simulated microgravity, the middle cerebral artery and mesenteric small artery were isolated and cannulated, the responses to increases of pressure and concentrations of vaso-constrictor were detected.(2) The second part of work was aim to examine the change of myogenic tone, the vasoconstriction and the vessel structure under electron microscope of middle cerebral artery and mesenteric small artery after a medium-term (28-day) simulated microgravity with and without 1-h/d -Gx countermeasure. After simulated microgravity, the middle cerebral artery and mesenteric small artery were isolated and cannulated, the responses to increases of pressure and concentrations of vaso-constrictor were detected, then fixed the vessel at in-situ length, the structure was examined with electronmicroscope.The main findings of the present work are as follows:(1) Simulated microgravity alone induced an enhancement of the myogenic tone and vasoconstrictor responsiveness in the isolated middle cerebral artery, increases the wall thiskness, the media thickness and the number of smooth muscle cell layers. Daily STD for 1 h prevented the changes of vessel structure, but did not prevent the functional enhancement in the middle cerebral artery. Compared with the simultaneous CON group, the myogenic tone and vasoconstriction to 5-HT of middle cerebral artery in SUS group (3-day) were increased 11.7%, 12.3%, respectively. In 28-day group, the myogenic tone and vasoconstriction to 5-HT of middle cerebral artery were increased 18.8 %, 13.7%, respectively. The wall thickness, the media thickness of middle cerebral artery in SUS group were increased by 56.4%(P<0.01), 63%(P<0.01), respectively, compared with that of in CON group. With 1h/d standing, the change of vessel structure can be prevented, but the increase of myogenic tone and vasoconstriction cannot be prevented.(2) Simulated microgravity alone induced an attenuation of the myogenic tone and vasoconstrictor responsiveness in the isolated mesenteric small artery, decreases the wall thiskness, the media thickness and the number of smooth muscle cell layers. Daily STD for 1 h can prevent the changes of vessel structure, and can also prevent the functional decrement in the mesenteric small artery. Compared with the simultaneous CON group, the myogenic tone and vasoconstriction to PE of mesenteric small artery in SUS group (3-day) were decreased 11.5%, 12.1%, respectively. In 28-day group, the myogenic tone and vasoconstriction to PE of mesenteric small artery were decreased 22.5%, 21.6%, respectively. The wall thickness, the media thickness of mesenteric small artery in SUS group were decreased by 20.0%(P<0.01), 28.6%(P<0.01), respectively, compared with that of in CON group. With 1h/d standing, not only the change of vessel structure can be prevented, but the decrease of myogenic tone and vasoconstriction can also be prevented.In conclusion, our working hypothesis has been supported by these above findings. Firstly, SUS alone induced an enhancement of the myogenic tone and vasoconstrictor responsiveness in the isolated middle cerebral artery but a depression of those in the mesenteric small artery. Secondly, the structure of middle cerebral artery and mesenteric small artery were changed by different effects. Daily standing for 1 h prevented the depression of myogenic tone and vasoconstrictor responsiveness in the mesenteric small artery, but did not prevent the functional enhancement in the middle cerebral artery. These data suggest that a short-term simulated microgravity may result in differential alterations in the function and structure of the cerebral artery and the resistance vessel in the hind-body. Both of the alteration of middle cerebral artery and mesenteric small artery can be prevented by 1h/d standing. However, only the functional changes in the mesenteric small arteries, not in the cerebral arteries, can be prevented by such a countermeasure of daily 1 h standing.
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