Angiotensin 1-7 Reduces Right Ventricular Hypertrophy and Fibrosis in a Rat Model of monocrotaline Induced Pulmonary Arterial Hypertension

Abstract

Background: Pulmonary arterial hypertension (PAH), characterized by high pressure in the pulmonary arteries, is fatal due to the development of right ventricular (RV) failure. Angiotensin-1-7 (Ang-(1-7)) is a metabolite of Angiotensin I/ II that has beneficial effects on pulmonary vascular remodelling in animal models of PAH. However its effect on RV myocardial remodelling in PAH is unknown.Objective: To study the effects of Ang-(1-7) on RV hypertrophy and fibrosis in an experimental PAH model.Methods: 220 gram Sprague-Dawley rats were randomized to: sham-controls (n=2), monocrotaline (MCT) induced PAH (n=3) and PAH + Ang-1-7 administered via subcutaneous injection for 5-weeks following injection of MCT (n=4). Animals were sacrificed at 5-weeks and the heart harvested for investigation of RV wall thickness and collagen content.Results: RV wall thickness was increased in the MCT-group (70.3  2.3 pixels vs. sham-controls 50.42  2.1 pixels p=0.0001) and decreased towards control values with the addition of Ang-(1-7) (52.7 1.9, p=0.0001 vs. MCT). RV myocardial collagen increased in the MCT-group (6.70.8 % vs. shams 2.70.2 %, p=0.0001) and decreased with the addition of Ang-(1-7) (5.60.2 %, p=0.04 vs. MCT).Conclusions: Ang-(1-7) reduces development of RV hypertrophy and fibrosis in MCT-induced PAH in rats, despite similar pulmonary arterial pressures. Further study is needed to investigate whether Ang-(1-7) improves RV performance and clinical outcomes in experimental and clinical settings.