Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardio-Pulmonary System (ECCPS), Member of the German Center for Lung Research (DZL), Aulweg 130, 35392, Giessen, Germany.
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
BMC Pulm Med. 2018 Mar 2;18(1):41. doi: 10.1186/s12890-018-0604-x.
Aldosterone is a mineralocorticoid hormone critically involved in arterial blood pressure regulation. Although pharmacological aldosterone antagonism reduces mortality and morbidity among patients with severe left-sided heart failure, the contribution of aldosterone to the pathobiology of pulmonary arterial hypertension (PAH) and right ventricular (RV) heart failure is not fully understood.
The effects of Eplerenone (0.1% Inspra® mixed in chow) on pulmonary vascular and RV remodeling were evaluated in mice with pulmonary hypertension (PH) caused by Sugen5416 injection with concomitant chronic hypoxia (SuHx) and in a second animal model with established RV dysfunction independent from lung remodeling through surgical pulmonary artery banding.
Preventive Eplerenone administration attenuated the development of PH and pathological remodeling of pulmonary arterioles. Therapeutic aldosterone antagonism - starting when RV dysfunction was established - normalized mineralocorticoid receptor gene expression in the right ventricle without direct effects on either RV structure (Cardiomyocyte hypertrophy, Fibrosis) or function (assessed by non-invasive echocardiography along with intra-cardiac pressure volume measurements), but significantly lowered systemic blood pressure.
Our data indicate that aldosterone antagonism with Eplerenone attenuates pulmonary vascular rather than RV remodeling in PAH.
醛固酮是一种参与动脉血压调节的关键激素。虽然药理醛固酮拮抗作用可降低严重左侧心力衰竭患者的死亡率和发病率，但醛固酮对肺动脉高压（PAH）和右心室（RV）心力衰竭的病理生物学的作用尚未完全了解。
通过 Sugen5416 注射联合慢性低氧（SuHx）引起的肺动脉高压（PH）小鼠和通过手术肺动脉缩窄建立的与肺重塑无关的 RV 功能障碍的第二个动物模型，评估依普利酮（0.1% Inspra®混入饲料）对肺血管和 RV 重塑的影响。
预防性依普利酮给药可减轻 PH 和肺小动脉病理性重塑的发生。开始于 RV 功能障碍时的治疗性醛固酮拮抗作用可使右心室中醛固酮受体基因表达正常化，而对 RV 结构（心肌细胞肥大，纤维化）或功能（通过非侵入性超声心动图以及心内压力容积测量进行评估）无直接影响，但可显著降低全身血压。
我们的数据表明，依普利酮的醛固酮拮抗作用可减轻 PAH 中的肺血管重塑，而不是 RV 重塑。
