Involvement of cyclo-oxygenase-1-mediated prostacyclin synthesis in the vasoconstrictor activity evoked by ACh in mouse arteries
Involvement of cyclo-oxygenase-1-mediated prostacyclin synthesis in the vasoconstrictor activity evoked by ACh in mouse arteries
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环加氧酶 1 介导的前列环素合成参与乙酰胆碱在小鼠动脉中引起的血管收缩活性
DOI：
10.1113/expphysiol.2011.062034
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发表时间：
2012-02-01
影响因子：
2.7
通讯作者：
Zhou, Yingbi
中科院分区：
文献类型：
--
作者：
Liu, Bin;Luo, Wenhong;Zhou, Yingbi
本研究旨在确定小鼠主动脉内皮细胞是否产生前列环素（PGI 2），如果是，则确定PGI 2如何影响血管反应性以及环氧化酶-1（考克斯-1）是否有助于PGI 2的合成。从野生型小鼠和/或具有考克斯-1或-2缺陷（考克斯-1-/-;考克斯-2-/-）的小鼠中分离腹部动脉、颈动脉和股动脉用于生物化学和/或功能分析。采用高效液相色谱-质谱法分析PGI 2代谢产物6-keto-PGF 1a，同时采用等长收缩力测量法测定血管反应性。结果表明，ACh可诱导腹主动脉内皮依赖性6-keto-PGF 1 a的产生，考克斯-1-/-可阻断ACh诱导的6-keto-PGF 1 a的产生，而考克斯-2-/-则不能阻断ACh诱导的6-keto-PGF 1 a的产生。有趣的是，考克斯-1-/-增强了对ACh的反应，而PGI 2引起肠系膜动脉舒张，引起收缩，通过拮抗腹主动脉中的血栓素前列腺素（TP）受体而消除收缩。然而，TP受体激动剂U46619在腹主动脉和肠系膜动脉中引起类似的收缩。此外，拮抗TP受体增强肠系膜动脉对PGI_2的舒张反应。实时荧光定量PCR显示腹主动脉PGI_2（IP）受体mRNA水平低于肠系膜动脉。此外，考克斯-1-/-不仅能抑制腹主动脉对ACh的收缩反应，还能抑制颈动脉和股动脉对ACh的收缩反应。这些结果表明内皮细胞考克斯-1在PGI 2合成中的明确作用，并表明在给定的小鼠动脉中，PGI 2介导的不是扩张而是血管收缩活性，这可能是由于IP受体的低表达或功能性存在，这使得PGI 2主要作用于TP受体。
This study was to determine whether the endothelium of mouse major arteries produces prostacyclin (PGI2) and, if so, to determine how PGI2 affects vasomotor reactivity and whether cyclo-oxygenase-1 (COX-1) contributes to PGI2 synthesis. Abdominal aortas, carotid and femoral arteries were isolated from wild-type mice and/or those with COX-1 or -2 deficiency (COX-1-/-; COX-2-/-) for biochemical and/or functional analyses. The PGI2 metabolite 6-keto-PGF1a was analysed with high-performance liquid chromatographymass spectroscopy, while vasoreactivity was determined with isometric force measurement. Results showed that in the abdominal aorta, ACh evoked endothelium-dependent production of 6-keto-PGF1a, which was abolished by COX-1-/-, but not by COX-2-/-. Interestingly, COX-1-/- enhanced the dilatation in response to ACh, while PGI2, which evoked relaxation of the mesenteric artery, caused contraction that was abolished by antagonizing thromboxane prostanoid (TP) receptors in the abdominal aorta. However, the TP receptor agonist U46619 evoked similar contractions in the abdominal aorta and mesenteric artery. Also, antagonizing TP receptors enhanced the relaxation in response to PGI2 in mesenteric arteries. Real-time PCR showed that the PGI2 (IP) receptor mRNA level was lower in the abdominal aorta than in mesenteric arteries. In addition, COX-1-/- not only abolished the contraction in response to ACh following NO inhibition in abdominal aorta, but also those in the carotid and femoral arteries. These results demonstrate an explicit role for endothelial COX-1 in PGI2 synthesis and suggest that in given mouse arteries, PGI2 mediates not dilatation but rather vasoconstrictor activity, possibly due to a low expression or functional presence of IP receptors, which enables PGI2 to act mainly on TP receptors.