Mitochondrial Oxidative Stress Enhances Vasoconstriction by Altering Calcium Homeostasis in Cerebrovascular Smooth Muscle Cells under Simulated Microgravity / 生物医学与环境科学（英文）

Objective@#Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries.@*Methods@#Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca @*Results@#An increase of cytoplasmic Ca @*Conclusion@#The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.

Time-course changes of myogenic tone of mesenteric small artery in spontaneously hypertensive rat / 生理学报

To investigate the time-course changes of myogenic tone in mesenteric small artery (MSA) of spontaneously hypertensive rat (SHR), thirty-two 7-week aged SHR rats were randomly divided into four groups (8, 16, 24, 32 weeks of age), and 32 sex- and age-matched Wistar-Kyoto (WKY) rats were assigned to control groups (CON). On the day of the study, segments of MSA were isolated and then cannulated to the two pipettes. Vascular diameters in response to the increased intraluminal pressure (from 0 mmHg to 150 mmHg, by 25 mmHg steps) of isolated MSA under no-flow conditions were recorded by a Pressure Myograph System both in physiologic salt solution (PSS) (active diameter, Da) and calcium-free PSS (passive diameter, Dp). The myogenic tone was calculated by (Dp - Da)/Dp × 100%. The tail artery pressure and vascular myogenic tone in SHR rats were significantly higher than those of the CON rats. Before 24 weeks, the vascular myogenic tone of MSA in SHR group increased monotonically, but at the end of 32 weeks, the vascular myogenic tone decreased in comparison with that in 24-week group, but was significantly higher than that in CON group. The tail artery pressure in SHR group slowly increased monotonically with increasing weeks of age, and the tail arterial pressure in 32-week group remained significantly higher than that in 24-week group. Vascular myogenic tone may participate in the whole process of hypertension. Early in the development of hypertension, because of the compensatory role of vascular tone, the vascular function has been partially compensated, thus guaranteeing adequate blood supply to organs. Late in the development of hypertension, because of the decompensation of myogenic tone, the vascular function is damaged, leading to the occurrence of severe vascular disease.

Earlier application of loading doses of aspirin and clopidogrel decreases rate of recurrent cardiovascular ischemic events for patients undergoing percutaneous coronary intervention / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aspirin and clopidogrel resistance plays a significant role in the development of cardiovascular ischemic events for ninety patients undergoing percutaneous coronary intervention. Recent studies have indicated that increasing the dose of antiplatelet drugs maybe a potent method to improve the inhibition of platelet aggregation.</p><p><b>METHODS</b>Thrombelastograph (TEG) determinations were used to evaluate the effect of antiplatelet therapy. According to the results, 90 patients were divided into three groups and given different doses of aspirin and clopidogrel. Thirty patients with both an inhibition rate of aspirin > 50% and an inhibition rate of clopidogrel > 50% were defined as the control group. Sixty patients with an inhibition rate for aspirin < 50% and an inhibition rate for clopidogrel < 50% were defined as the resistance group. Patients in resistance group were randomly assigned to be given a routine dose (100 mg aspirin plus 75 mg clopidogrel per day, which we called a resistance plus routine dose group, R + R) and a loading dose (200 mg aspirin and 150 mg clopidogrel per day, which we called resistance plus loading dose group, R + L) of antiplatelet therapy. A 12-month follow-up was observed to examine the change of inhibition rate of antiplatelet therapy and to estimate the relationship between inhibition rate and the occurrence of cardiovascular ischemic events.</p><p><b>RESULTS</b>After 6 months of antiplatelet therapy, the inhibition rate of aspirin in the R + L group increased from (31.4 ± 3.7)% to (68.6 ± 7.1)%, which was significantly higher than that in R + R group, (51.9 ± 8.2)% (P < 0.01). The inhibition rate of clopidogrel in the R + L group increased from (22.1 ± 3.8)% to (60.2 ± 7.4)%, which was significantly higher than in the R + R group, (45.9 ± 4.3)% (P < 0.01). The occurrence rates of cardiovascular ischemic events, stent thrombosis, recurrent unstable angina and myocardial infarction in the R + R group were 20%, 36% and 17%, respectively. Occurrence was significantly increased compared with that in the control group, 3%, 10% and 1%, respectively (P < 0.01). In contrast, the occurrence rates in the R + L group (10%, 23% and 6%, respectively) were attenuated compared with those in the R + R group (P < 0.01), although still higher than in the control group (P < 0.01).</p><p><b>CONCLUSIONS</b>Almost all of the cardiovascular ischemic events occurred in the first six months after percutaneous coronary intervention. According to the result of TEG determinations, earlier application of a loading dose of aspirin and clopidogrel can decrease the rate of recurrent cardiovascular ischemic events.</p>

Differential effect of simulated microgravity on myogenic tone of middle cerebral and mesenteric small arteries in rats / 生理学报

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. Segments of middle cerebral artery and mesenteric third-order small artery were isolated and cannulated. Vascular diameters in response to increased intraluminal pressure (from 20 mmHg to 120 mmHg, by 20 mmHg steps) of isolated arteries under no-flow conditions were recorded by a Pressure Myograph System in both physiologic salt solution (PSS) (active diameter, Da) and calcium-free PSS (passive diameter, Dp). The myogenic tone was calculated by (Dp-Da)/Dpx100%. Vasoconstrictor responsiveness of the isolated middle cerebral artery to serotonin and that of small mesenteric artery to phenylephrine were assessed in the PSS under an intraluminal pressure of 40 mmHg. The results showed that SUS induced an enhancement of the myogenic tone and vasoconstrictor responsiveness in the isolated middle cerebral artery but a depression of those in the small mesenteric artery. Daily STD for 1 h prevented the depression of myogenic tone and vasoconstrictor responsiveness in the small mesenteric 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 different alterations in the function of the cerebral artery and the resistance vessel in the hind-body. Moreover, only the decrease of function in these resistance vessels, not in the cerebral arteries, can be prevented by such a countermeasure of daily STD for 1 h.

Comparison of biomechanical behavior of cerebral and mesenteric small arteries of simulated microgravity rats / 生理学报

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)). Results from the analysis of active biomechanical properties revealed the contribution of vascular smooth muscle (VSM) tone during the early adaptation to microgravity: (1) For mesenteric small arteries, active circumferential sigma(theta) -epsilon(theta) curve of SUS group was comparable with that of the passive vessels, indicating that the function of VSM to restore the normal stress distribution is compromised; however, this mal-adaptation was fully prevented by the countermeasure of daily 1 h of -G(x) gravitation; (2) For the middle cerebral arteries, active circumferential sigma(theta) -epsilon(theta) relation of SUS group was shifted to the left side of the passive curve and epsilon(theta) was kept at a nearly constant level with the corresponding sigma(theta) being at its normal range; furthermore, the enhanced myogenic tone responsiveness was not prevented by daily short-duration -G(x). Analysis of the passive biomechanical properties has suggested remodeling changes in matrix components of different types of vessels, which might be significant if the exposure duration was further prolonged. In brief, studies of vascular biomechanics are of particular importance in elucidating the mechanisms underlying vascular adaptation to microgravity and its gravity-based countermeasure.