Yang Cui, Xu Yinyan, Mendez Tavis, Wang Fang, Yang Qin, Li Shengnan
Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
Vascul Pharmacol. 2006 Apr;44(4):238-46. doi: 10.1016/j.vph.2006.01.001. Epub 2006 Feb 20.
We investigated the relationship between urocortin and the activity of angiotensin-converting enzyme (ACE), which plays a key role in producing the potent vasoconstrictor angiotensin II (Ang II). Urocortin was acutely and subchronically administered to Sprague-Dawley (SD) rats and then the serum and tissue (lung and aorta) ACE levels were evaluated. The tissue ACE mRNA was determined by using reverse transcription and polymerase chain reaction (RT-PCR) analysis. Immunofluorescence studies were also preformed to evaluate the effect of urocortin on ACE in cultured rat aortic endothelial cells (RAECs). Urocortin decreased the serum ACE level 1h after administration, whereas tissue ACE immunoreactivity and mRNA did not change. The prolonged administration of urocortin enhanced tissue ACE activity but the serum ACE level remained low. RT-PCR analysis showed that tissue ACE mRNA was elevated. Immunofluorescence studies also demonstrated an increase of ACE intensity in RAECs exposed to urocortin for 72 h. Corticotropin-releasing factor (CRF) receptor blocker, astressin, abolished the effects of urocortin. Extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker, PD98059, also markedly inhibited these effects, suggesting urocortin affects the activity of ACE through the ERK1/2 pathway in rats. These findings support the changes in mean arterial pressure (MAP) following acute and subchronic injections of urocortin in previous studies. Thus, the changes of the ACE activity and its production of Ang II may play a role in the vasodilatory property of urocortin.
我们研究了尿皮质素与血管紧张素转换酶（ACE）活性之间的关系，ACE在强效血管收缩剂血管紧张素II（Ang II）的产生中起关键作用。对Sprague-Dawley（SD）大鼠进行急性和亚慢性尿皮质素给药，然后评估血清和组织（肺和主动脉）中的ACE水平。通过逆转录和聚合酶链反应（RT-PCR）分析测定组织ACE mRNA。还进行了免疫荧光研究，以评估尿皮质素对培养的大鼠主动脉内皮细胞（RAECs）中ACE的影响。尿皮质素给药1小时后血清ACE水平降低，而组织ACE免疫反应性和mRNA未发生变化。尿皮质素的长期给药增强了组织ACE活性，但血清ACE水平仍然较低。RT-PCR分析显示组织ACE mRNA升高。免疫荧光研究还表明，暴露于尿皮质素72小时的RAECs中ACE强度增加。促肾上腺皮质激素释放因子（CRF）受体阻滞剂阿斯特辛消除了尿皮质素的作用。细胞外信号调节激酶1/2（ERK1/2）通路阻滞剂PD98059也显著抑制了这些作用，表明尿皮质素通过ERK1/2通路影响大鼠体内ACE的活性。这些发现支持了先前研究中急性和亚慢性注射尿皮质素后平均动脉压（MAP）的变化。因此，ACE活性及其Ang II产生的变化可能在尿皮质素的血管舒张特性中起作用。
