Sangha D S, Vaziri N D, Ding Y, Purdy R E
Department of Pharmacology, College of Medicine, University of California, Irvine, California 92697-4625, USA.
J Appl Physiol (1985). 2000 Feb;88(2):507-17. doi: 10.1152/jappl.2000.88.2.507.
Simulated microgravity depresses the ability of arteries to constrict to norepinephrine (NE). In the present study the role of nitric oxide-dependent mechanisms on the vascular hyporesponsiveness to NE was investigated in peripheral arteries of the rat after 20 days of hindlimb unweighting (HU). Blood vessels from control rats and rats subjected to HU (HU rats) were cut into 3-mm rings and mounted in tissue baths for the measurement of isometric contraction. Mechanical removal of the endothelium from carotid artery rings, but not from aorta or femoral artery rings, of HU rats restored the contractile response to NE toward control. A 10-fold increase in sensitivity to ACh was observed in phenylephrine-precontracted carotid artery rings from HU rats. In the presence of the nitric oxide synthase (NOS) substrate L-arginine, the inducible NOS inhibitor aminoguanidine (AG) restored the contractile responses to NE to control levels in the femoral, but not carotid, artery rings from HU rats. In vivo blood pressure measurements revealed that the peak blood pressure increase to NE was significantly greater in the control than in the HU rats, but that to AG was less than one-half in control compared with HU rats. These results indicate that the endothelial vasodilator mechanisms may be upregulated in the carotid artery, whereas the inducible NOS expression/activity may be increased in the femoral artery from HU rats. These HU-mediated changes could produce a sustained elevation of vascular nitric oxide levels that, in turn, could contribute to the vascular hyporesponsiveness to NE.
模拟微重力会降低动脉对去甲肾上腺素（NE）的收缩能力。在本研究中，我们调查了在大鼠后肢去负荷（HU）20天后，一氧化氮依赖性机制在血管对NE反应性降低中的作用。将对照大鼠和接受HU处理的大鼠（HU大鼠）的血管切成3毫米的环，并安装在组织浴中以测量等长收缩。机械去除HU大鼠颈动脉环的内皮，但不去除主动脉或股动脉环的内皮，可使对NE的收缩反应恢复到对照水平。在HU大鼠的苯肾上腺素预收缩颈动脉环中，观察到对乙酰胆碱的敏感性增加了10倍。在存在一氧化氮合酶（NOS）底物L-精氨酸的情况下，诱导型NOS抑制剂氨基胍（AG）可使HU大鼠股动脉环（而非颈动脉环）对NE的收缩反应恢复到对照水平。体内血压测量显示，对照大鼠中NE引起的血压峰值升高明显大于HU大鼠，但与HU大鼠相比，对照大鼠中AG引起的血压峰值升高不到一半。这些结果表明，HU大鼠颈动脉中的内皮舒张机制可能上调，而股动脉中的诱导型NOS表达/活性可能增加。这些由HU介导的变化可能导致血管一氧化氮水平持续升高，进而导致血管对NE反应性降低。
