NO CONTRIBUTES TO ABNORMAL VASCULAR CALCIUM REGULATION AND REACTIVITY INDUCED BY PERITONITIS-ASSOCIATED SEPTIC SHOCK IN RATS
NO CONTRIBUTES TO ABNORMAL VASCULAR CALCIUM REGULATION AND REACTIVITY INDUCED BY PERITONITIS-ASSOCIATED SEPTIC SHOCK IN RATS
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DOI：
10.1097/shk.0b013e3181bea334
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发表时间：
2010-05-01
期刊：
影响因子：
3.1
通讯作者：
Wu, Chin-Chen
中科院分区：
文献类型：
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作者：
Chen, Shiu-Jen;Li, Shaio-Yun;Wu, Chin-Chen
钙在决定血管平滑肌张力中起重要作用。去甲肾上腺素（NE）诱导的血管收缩包含两个组成部分：1）作为快相的肌浆网的Ca 2+释放和2）作为慢相的通过电压依赖性钙通道的Ca 2+内流。本研究采用功能性等长张力记录，以评估介导异常NE诱导的Ca2+处理和反应性在离体的胸腔积液脓毒症大鼠。盲肠结扎穿孔法（CLP）诱导脓毒症，CLP后18 h取胸段肠管。我们的研究结果表明，大鼠接受CLP 18小时表现出严重的低血压和血管对NE的低反应性在体内。在CLP诱导的脓毒症大鼠的主动脉中也观察到这种血管对NE的低反应性。脓毒症大鼠膈肌NE收缩的快、慢相均减少。为了阐明哪些可能的介质导致脓毒症动物腹膜炎中的异常Ca2+处理，使用了Ca2+通道和释放的抑制剂。抑制2-氨基乙氧基-二苯基硼烷，ryanodine，和cyclopiazonic酸的NE诱导的收缩在无钙溶液中是更大的脓毒症大鼠的主动脉和抑制cyclopiazonic酸和ryanodine，但不是2-氨基乙氧基-二苯基硼烷，减弱NOS抑制剂N-ω-硝基-L-精氨酸甲酯。此外，CLP组中硝苯地平对NE诱导的主动脉收缩的衰减也更大。我们的研究结果表明，异常NE诱导的Ca2+处理与血管低反应性CLP诱导的脓毒症是由肌浆网功能的重大下降和轻微损害的电压依赖性Ca2+通道膜上的Ca2+处理，至少在主动脉，这可能是由于在脓毒症的NO的过度生产。
Calcium plays an important role in determining vascular smooth muscle tone. Norepinephrine (NE)-induced vascular contraction contains two components: 1) Ca2+ release from the sarcoplasmic reticulum as the fast phase and 2) Ca2+ influx via a voltage-dependent calcium channel as the slow phase. This study used functional isometric tension recording to evaluate mediators contributing to abnormal NE-induced Ca2+ handling and reactivity in isolated thoracic aortas from septic rats. Sepsis was induced by cecal ligation and puncture (CLP), and thoracic aortas were removed at 18 h after CLP. Our results showed that rats that received CLP for 18 h manifested severe hypotension and vascular hyporeactivity to NE in vivo. This vascular hyporecativity to NE was also observed in the aorta obtained from CLP-induced sepsis rat. Both the fast and slow phases of NE-induced contraction were reduced in aortas from sepsis rats. To clarify what possible mediators contribute to the abnormal Ca2+ handling in aortas from sepsis animals, inhibitors of Ca2+ channel and release were used. Inhibition by 2-aminoethoxy-diphenyl borane, ryanodine, and cyclopiazonic acid of the NE-induced contraction in Ca2+-free solution was greater in the aorta from sepsis rats and inhibitions of cyclopiazonic acid and ryanodine, but not of 2-aminoethoxy-diphenyl borane, were attenuated by NOS inhibitor N-omega-nitro-L-arginine methyl ester. In addition, the attenuation of NE-induced contraction by nifedipine in the aorta was also greater in the CLP group. Our results suggest that abnormal NE-induced Ca2+ handling associated with vascular hyporeactivity in the CLP-induced sepsis is caused by a major decrease in sarcoplasmic reticulum function and a minor impairment of voltage-dependent Ca2+ channels on membrane to Ca2+ handling, at least, in the aorta, and this could be attributed to an overproduction of NO in sepsis.