Cardiovascular Research Center, Shantou University College of Medicine, 22 Xin-Ling Road, Shantou, China 515041.
Exp Physiol. 2012 Feb;97(2):277-89. doi: 10.1113/expphysiol.2011.062034. Epub 2011 Nov 11.
This study was to determine whether the endothelium of mouse major arteries produces prostacyclin (PGI(2)) and, if so, to determine how PGI(2) affects vasomotor reactivity and whether cyclo-oxygenase-1 (COX-1) contributes to PGI(2) 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 PGI(2) metabolite 6-keto-PGF(1α) was analysed with high-performance liquid chromatography-mass spectroscopy, while vasoreactivity was determined with isometric force measurement. Results showed that in the abdominal aorta, ACh evoked endothelium-dependent production of 6-keto-PGF(1α), which was abolished by COX-1(-/-), but not by COX-2(-/-). Interestingly, COX-1(-/-) enhanced the dilatation in response to ACh, while PGI(2), 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 PGI(2) in mesenteric arteries. Real-time PCR showed that the PGI(2) (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 PGI(2) synthesis and suggest that in given mouse arteries, PGI(2) mediates not dilatation but rather vasoconstrictor activity, possibly due to a low expression or functional presence of IP receptors, which enables PGI(2) to act mainly on TP receptors.
这项研究旨在确定小鼠主要动脉的内皮细胞是否产生前列环素（PGI2），如果是，确定 PGI2 如何影响血管舒缩反应，以及环氧化酶-1（COX-1）是否有助于 PGI2 的合成。从野生型小鼠和/或 COX-1 或 -2 缺陷（COX-1（-/-）；COX-2（-/-））中分离出腹主动脉、颈动脉和股动脉，用于生化和/或功能分析。使用高效液相色谱-质谱法分析 PGI2 代谢物 6-酮-PGF1α，同时使用等长力测量法测定血管反应性。结果表明，在腹主动脉中，ACh 诱发内皮依赖性产生 6-酮-PGF1α，该反应被 COX-1（-/-）消除，但不受 COX-2（-/-）影响。有趣的是，COX-1（-/-）增强了对 ACh 的扩张反应，而 PGI2 引起肠系膜动脉舒张，引起收缩，该收缩在腹主动脉中拮抗血栓素前列腺素（TP）受体后被消除。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 受体增强了肠系膜动脉对 PGI2 的舒张反应。实时 PCR 显示，PGI2（IP）受体 mRNA 水平在腹主动脉中低于肠系膜动脉。此外，COX-1（-/-）不仅消除了 NO 抑制后腹主动脉对 ACh 的收缩反应，还消除了颈动脉和股动脉的收缩反应。这些结果表明内皮 COX-1 在 PGI2 合成中具有明确的作用，并表明在特定的小鼠动脉中，PGI2 介导的不是扩张而是血管收缩活性，可能是由于 IP 受体的低表达或功能存在，这使得 PGI2 主要作用于 TP 受体。
