SMOOTH-MUSCLE CELL-DERIVED CARBON-MONOXIDE IS A REGULATOR OF VASCULAR CGMP
SMOOTH-MUSCLE CELL-DERIVED CARBON-MONOXIDE IS A REGULATOR OF VASCULAR CGMP
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DOI：
10.1073/pnas.92.5.1475
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发表时间：
1995-02-28
影响因子：
11.1
通讯作者：
KOUREMBANAS, S
中科院分区：
文献类型：
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作者：
MORITA, T;PERRELLA, MA;KOUREMBANAS, S
一氧化碳（GO）是血红素加氧酶（HO; EC www.example.com）的产物1.14.99.3。在血管平滑肌细胞中，外源性给予CO增加环鸟苷3 '，5'-单磷酸（cGMP），这是血管张力的重要调节剂。我们在这里报告平滑肌细胞通过HO产生CO，并且它调节这些细胞中的cGMP水平。显著增加HO-1基因的转录速率，导致其mRNA和HO酶活性相应增加。此外，在相同条件下，大鼠主动脉和肺动脉平滑肌细胞积累高水平的cGMP，其时间过程与HO-1产生的时间过程相似。平滑肌细胞中cGMP积累的增加需要HO的酶活性，因为它被特异性HO抑制剂锡原卟啉消除。相反，N-ω-硝基-L-精氨酸，一氧化氮（NO）合成的有效抑制剂，没有影响cGMP产生的平滑肌细胞，表明NO是不负责的鸟苷酸环化酶的激活在这种情况下，此外，缺氧平滑肌细胞的条件培养基刺激受体细胞的cGMP生产和这种刺激。分别被一氧化碳产生抑制剂和一氧化碳清除剂锡原卟啉或血红蛋白完全抑制。本报告表明HO-1由血管平滑肌细胞表达，其产物一氧化碳可以调节生理和病理生理（如缺氧）条件下的血管张力。
Carbon monoxide (GO) is a product of the enzyme heme oxygenase (HO; EC 1.14.99.3), In vascular smooth muscle cells, exogenously administered CO increases cyclic guanosine 3',5'-monophosphate (cGMP), which is an important regulator of vessel tone, We report here that smooth muscle cells produce CO via HO and that it regulates cGMP levels in these tells, Hypoxia, which has profound effects on vessel tone, significantly increased the transcriptional rate of the HO-1 gene resulting in corresponding increases of its mRNA and HO enzymatic activity, In addition, under the same conditions, rat aortic and pulmonary artery smooth muscle cells accumulated high levels of cGMP following a similar time course to that of HO-1 production, The increased accumulation of cGMP in smooth muscle cells required the enzymatic activity of HO, since it was abolished by a specific HO inhibitor, tin protoporphyrin, In contrast, N-omega-nitro-L-arginine, a potent inhibitor of nitric oxide (NO) synthesis, had no effect an cGMP produced by smooth muscle cells, indicating that NO is not responsible for the activation of guanylyl cyclase in this setting, Furthermore, conditioned medium from hypoxic smooth muscle cells stimulated cGMP production in recipient cells and this stimulation. was completely inhibited by tin protoporphyrin or hemoglobin, an inhibitor of CO production and a scavenger of CO, respectively, This report shows that HO-1 is expressed by vascular smooth muscle cells and that its product, CO, may regulate vascular tone under physiologic and pathophysiologic (such as hypoxic) conditions.