Mineralocorticoid receptor antagonism protects the aorta from vascular smooth muscle cell proliferation and collagen deposition in a rat model of adrenal aldosterone-producing adenoma

• Yongji Yan ^[1] ; Chao Wang ^[2] ; Yiqin Lu ^[3] ; Huijie Gong ^[1] ; Zhun Wu ^[4] ; Xin Ma ^[5] ; Hongzhao Li ^[5] ; Baojun Wang ^[5] ; Xu Zhang ^[5]
  1. [1] Dongzhimen Hospital Affiliated to Beijing University of Chinese MedicineBeijingPeople’s Republic of China
  2. [2] First People’s Hospital of Jining CityJiningPeople’s Republic of China
  3. [3] First People’s Hospital of Yunnan ProvinceKunmingPeople’s Republic of China
  4. [4] First Affiliated Hospital of Xiamen UniversityXiamenPeople’s Republic of China
  5. [5] Chinese People’s Liberation Army General HospitalMilitary Postgraduate Medical CollegeBeijingPeople’s Republic of China

  Mostrar afiliaciones +
• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 74, Nº. 1, 2018, págs. 17-24
• Idioma: inglés
• Enlaces
  • Texto completo (pdf)
• Resumen

  • The number of patients with adrenal aldosterone-producing adenomas (APAs) has gradually increased. However, even after adenoma resection, some patients still suffer from high systolic blood pressure (SBP), which is possibly due to great arterial remodeling. Moreover, mineralocorticoid receptors (MRs) were found to be expressed in vascular smooth muscle cells (VSMCs). This study aims to determine whether MR antagonism protects the aorta from aldosterone-induced aortic remolding. Male rats were subcutaneously implanted with an osmotic minipumps and randomly divided into four groups: control; aldosterone (1 μg/h); aldosterone plus a specific MR antagonist, eplerenone (100 mg/kg/day); and aldosterone plus a vasodilator, hydralazine (25 mg/kg/day). After 8 weeks of infusion, aortic smooth muscle cell proliferation and collagen deposition, as well as the MDM2 and TGF-β1 expression levels in the aorta, were examined. Model rats with APAs were successfully constructed. Compared with the control rats, the model rats exhibited (1) marked SBP elevation, (2) no significant alteration in aortic morphology, (3) increased VSMC proliferation and MDM2 expression in the aorta, and (4) enhanced total collagen and collagen III depositions in the aorta, accompanied with up-regulated expression of TGF-β1. These effects were significantly inhibited by co-administration with eplerenone but not with hydralazine. These findings suggested that specific MR antagonism protects the aorta from aldosterone-induced VSMC proliferation and collagen deposition.