Prisby Rhonda D, Wilkerson M Keith, Sokoya Elke M, Bryan Robert M, Wilson Emily, Delp Michael D
Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia 26506, USA.
J Appl Physiol (1985). 2006 Jul;101(1):348-53. doi: 10.1152/japplphysiol.00941.2005. Epub 2006 Apr 20.
Cephalic elevations in arterial pressure associated with microgravity and prolonged bed rest alter cerebrovascular autoregulation in humans. Using the head-down tail-suspended (HDT) rat to chronically induce headward fluid shifts and elevate cerebral artery pressure, previous work has likewise shown cerebral perfusion to be diminished. The purpose of this study was to test the hypothesis that 2 wk of HDT reduces cerebral artery vasodilation. To test this hypothesis, dose-response relations for endothelium-dependent (2-methylthioadenosine triphosphate and bradykinin) and endothelium-independent (nitroprusside) vasodilation were determined in vitro in middle cerebral arteries (MCAs) from HDT and control rats. All in vitro measurements were done in the presence and absence of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (10(-5) M) and cyclooxygenase inhibitor indomethacin (10(-5) M). MCA caveolin-1 protein content was measured by immunoblot analysis. Endothelium-dependent vasodilation to 2-methylthioadenosine triphosphate and bradykinin were both lower in MCAs from HDT rats. These lower vasodilator responses were abolished with N(G)-nitro-L-arginine methyl ester but were unaffected by indomethacin. In addition, HDT was associated with lower levels of MCA caveolin-1 protein. Endothelium-independent vasodilation was not altered by HDT. These results indicate that chronic cephalic fluid shifts diminish endothelium-dependent vasodilation through alterations in the endothelial nitric oxide synthase signaling mechanism. Such decrements in endothelium-dependent vasodilation of cerebral arteries could contribute to the elevations in cerebral vascular resistance and reductions in cerebral perfusion that occur after conditions of simulated microgravity in HDT rats.
与微重力和长期卧床休息相关的动脉压头向升高会改变人类的脑血管自动调节功能。利用头低位尾悬吊（HDT）大鼠来长期诱导头向液体转移并升高脑动脉压，先前的研究同样表明脑灌注会减少。本研究的目的是检验以下假设：2周的HDT会降低脑动脉血管舒张功能。为了验证这一假设，在体外测定了HDT大鼠和对照大鼠大脑中动脉（MCA）对内皮依赖性（2-甲硫基三磷酸腺苷和缓激肽）和非内皮依赖性（硝普钠）血管舒张的剂量反应关系。所有体外测量均在存在和不存在一氧化氮合酶抑制剂N(G)-硝基-L-精氨酸甲酯（10(-5) M）和环氧化酶抑制剂吲哚美辛（10(-5) M）的情况下进行。通过免疫印迹分析测量MCA小窝蛋白-1的含量。HDT大鼠MCA对2-甲硫基三磷酸腺苷和缓激肽的内皮依赖性血管舒张均较低。这些较低的血管舒张反应被N(G)-硝基-L-精氨酸甲酯消除，但不受吲哚美辛影响。此外，HDT与MCA小窝蛋白-1蛋白水平降低有关。HDT未改变非内皮依赖性血管舒张。这些结果表明，慢性头向液体转移通过改变内皮一氧化氮合酶信号机制来减少内皮依赖性血管舒张。脑动脉内皮依赖性血管舒张的这种降低可能导致HDT大鼠模拟微重力条件后脑血管阻力升高和脑灌注减少。
