Aldosterone Contributed to Pulmonary Arterial Hypertension Development via Stimulating Aquaporin Expression and Pulmonary Arterial Smooth Muscle Cells Proliferation.

Introduction and Objective:The regulatory network of aquaporin (AQP) 1 and renin-angiotensin-aldosterone (ALDO) system are not quite clear in pulmonary arterial hypertension (PAH). Thus, we explored the role of AQP1, ALDO and spirolactone (SP) in the PAH animal model and pulmonary arterial smooth muscle cells (PASMCs).Method:PAH rat model was established by monocrotaline (MCT) via intraperitoneal in SD rat. Hemodynamic measurement was conducted via the external jugular vein cannula. PASMCs were extracted from normal SD rat and cultured in SmGM medium. alpha-Actin expression was identified by immunocytochemistry. Protein levels were assessed by Western blot. Cell viability was assayed using the MTT method. Apoptosis rate was evaluated by flow cytometry. ALDO level was measured by ELISA.Result:SP decreased AQP1 and beta-catenin expressions in PAH rat model induced successfully by MCT. Moreover, ALDO increased AQP1 expression and cell viability in PASMCs, which were extracted from rat and identified by alpha-actin expression. AQP1 downregulation decreased beta-catenin expression, and SP lowered AQP1 and beta-catenin expressions elevated by ALDO in PASMCs. SP offset ALDO's effect on the upregulation of cell viability as well as AQP1 and beta-catenin expressions in PASMCs. In addition, AQP1 downregulation and SP have a negative effect on Ki-67 and proliferating cell nuclear antigen expressions as well as cell viability after ALDO treatment in PASMCs.Conclusion:ALDO might contribute to PAH development via stimulating AQP1 expression and PASMCs proliferation. However, SP could be considered an effective drug regulating PASMCs proliferation through modulating AQP1 and beta-catenin expressions in PAH.