Cyclooxygenase-2–Derived Prostaglandin F2 Mediates Endothelium-Dependent Contractions in the Aortae of Hamsters With Increased Impact During Aging
Cyclooxygenase-2–Derived Prostaglandin F2 Mediates Endothelium-Dependent Contractions in the Aortae of Hamsters With Increased Impact During Aging
复制标题
DOI：
10.1161/circresaha.108.179770
复制
发表时间：
2009-01
影响因子：
20.1
通讯作者：
Siu Ling Wong;F. Leung;C. Lau;C. Au;L. Yung;X. Yao;Zhen-Yu Chen;P. Vanhoutte;M. Gollasch
中科院分区：
文献类型：
--
作者：
Siu Ling Wong;F. Leung;C. Lau;C. Au;L. Yung;X. Yao;Zhen-Yu Chen;P. Vanhoutte;M. Gollasch
高血压和血管功能障碍导致内皮源性收缩因子（EDCF）释放增加，其身份定义不清。我们验证了内皮环氧合酶（考克斯）-2可以产生EDCF的假设，并确定了可能的EDCF候选者。用肌电描记仪记录了青年和老年金黄地鼠股骨头等长收缩张力的变化。通过成像测量天然主动脉内皮细胞中细胞内钙浓度（[Ca 2 +]i）的实时变化。内皮依赖性收缩被乙酰胆碱（ACh）触发后，抑制一氧化氮的产生，他们被取消的考克斯-2，但不是考克斯-1抑制剂或血栓烷前列腺素受体拮抗剂。2-氨基乙氧基二苯基硼酸盐（阳离子通道阻断剂）消除内皮依赖性收缩和ACh刺激的内皮细胞[Ca ~（2+）]i升高。RT-PCR和Western blotting显示考克斯-2主要表达于内皮细胞。酶免疫分析和高效液相色谱-质谱联用显示释放的前列腺素（PG）F2和前列环素（PGI 2）增加乙酰胆碱;只有PGF 2引起收缩在相关浓度。考克斯-2的表达，乙酰胆碱刺激的收缩，血管对前列腺素F2的敏感性增加，从老年仓鼠睾丸。人肾动脉也表现出血栓素-前列腺素受体介导的ACh-或PGF 2-诱导的收缩和考克斯-2依赖性的PGF 2释放。目前的研究表明，PGF 2，来自考克斯-2，这是主要定位在内皮，是最有可能的EDCF的基础内皮依赖性，血栓素-前列腺素受体介导的收缩，以乙酰胆碱在仓鼠盲肠。这些收缩涉及内皮细胞[Ca 2 +]i的增加。结果支持考克斯-2在该物种的内皮依赖性收缩中的关键作用，在衰老过程中重要性增加，并且可能在人类中具有类似的相关性。
Hypertension and vascular dysfunction result in the increased release of endothelium-derived contracting factors (EDCFs), whose identity is poorly defined. We tested the hypothesis that endothelial cyclooxygenase (COX)-2 can generate EDCFs and identified the possible EDCF candidate. Changes in isometric tension of aortae of young and aged hamsters were recorded on myograph. Real-time changes in intracellular calcium concentrations ([Ca2+]i) in native aortic endothelial cells were measured by imaging. Endothelium-dependent contractions were triggered by acetylcholine (ACh) after inhibition of nitric oxide production and they were abolished by COX-2 but not COX-1 inhibitors or by thromboxane–prostanoid receptor antagonists. 2-Aminoethoxydiphenyl borate (cation channel blocker) eliminated endothelium-dependent contractions and ACh-stimulated rises in endothelial cell [Ca2+]i. RT-PCR and Western blotting showed COX-2 expression mainly in the endothelium. Enzyme immunoassay and high-performance liquid chromatography-coupled mass spectrometry showed release of prostaglandin (PG)F2 and prostacyclin (PGI2) increased by ACh; only PGF2 caused contraction at relevant concentrations. COX-2 expression, ACh-stimulated contractions, and vascular sensitivity to PGF2 were augmented in aortae from aged hamsters. Human renal arteries also showed thromboxane–prostanoid receptor–mediated ACh- or PGF2-induced contractions and COX-2–dependent release of PGF2. The present study demonstrates that PGF2, derived from COX-2, which is localized primarily in the endothelium, is the most likely EDCF underlying endothelium-dependent, thromboxane–prostanoid receptor–mediated contractions to ACh in hamster aortae. These contractions involved increases in endothelial cell [Ca2+]i. The results support a critical role of COX-2 in endothelium-dependent contractions in this species with an increased importance during aging and, possibly, a similar relevance in humans.