Protective Effect and Mechanism of Alprostadil in Acute Respiratory Distress Syndrome Induced by Oleic Acid in Rats

Yan, Xiujuan; Li, Yingxiu; Choi, Yun Ho; Wang, Chongyang; Piao, Yihua; Ye, Jing; Jiang, Jingzhi; Li, Liangchang; Xu, Huixian; Cui, Qingsong; Yan, Guanghai; Jin, Minggen

In recent decades, RAS has been thought to be essential in maintaining blood pressure homeostasis, as well as fluid and salt balance [16] . The latest evidence suggested that activation of the pulmonary RAS can influence the pathogenesis of ARDS via such mechanisms as inflammation, vascular permeability, vascular tone, and fibroblast activity [58] . ACE is a key member of the classical renin-angiotensin system. The lungs are major organs that express ACE in humans and rats. The importance of RAS in ARDS has been widely emphasized. Idell et al. [58] found that ARDS patients had elevated ACE levels in bronchoalveolar lavage. Orfanos [59] also reported that pulmonary capillary endothelium-bound ACE activity was correlated with the severity of lung injury in patients with acute respiratory distress syndrome. In the present study, we used Western blot and immunohistochemistry to examine the expression of ACE, a lung-injury-promoting factor in ALI, in lung tissues to assess the degree of lung injury. We found that OA administration caused a significant increase in the expression of ACE in the lung tissues when compared with the control group, suggesting that ACE and ARDS have a significant correlation. It could be speculated that injection of OA aggravates lung injury, and the unceasingly increased ACE in the lungs would increase the RAS activity in the lungs. ACE may cause pulmonary vasoconstriction and pulmonary arterial pressure upgrading, as well as increasing pneumoangiogram permeability via increased RAS activity. In addition, ACE may promote the infiltration of monocytes/macrophages and promote inflammatory factor secretion, leading to more severe lung injury and the formation of pulmonary hypertension and fibrosis [60] . However, the upregulated ACE expression was significantly reversed by alprostadil treatment. These results suggest that the lung RAS participates in this injury process.