Efeitos da Angiotensina - (1-7) na função cardíaca do ventrículo direito e no remodelamento vascular em suínos com hipertensão pulmonar induzida

Abstract

Pulmonary arterial hypertension is a complex condition characterized by endothelial dysfunction and elevated pressure in the pulmonary vasculature. To date, there is no cure for the condition and the goal of treatment is to promote relief of symptoms, increase survival, and improve patients' quality of life. However, conventional therapy is unsatisfactory and the development of new therapeutic methods is necessary. Recent studies have proposed that angiotensin- (1-7) exert dilating effects on vascular beds and also decrease vascular remodeling, being these potential beneficial factors for the treatment of pulmonary hypertension. This study aims to study the therapeutic potential of angiontensin (1-7) in animals with monocrotalin-induced pulmonary hypertension. The experiment was carried out on 14 pigs. At 40 days of age, the animals were evaluated by means of electrocardiography, echocardiography, systemic systolic blood pressure and serum concentration, brain natriuretic peptide and nitric oxide, and then received monocrotaline intravenously inducing the lesion. Subsequently, they were divided into two groups (n = 7). The first group received Angiotensin - (1-7) and the second placebo throughout the study. The animals were submitted to daily physical examination in the bays and the complementary exams were repeated monthly. At the end of 60 days they were euthanized and had fragments of the heart and lungs collected for histopathological analysis. The placebo group had electrocardiographic changes (increased T-wave amplitude, QT interval and left-sided cardiac axis) and higher systolic blood pressure at 60 days (GP 97.57 ± 13.36 and GT 87.14 ± 10.45). In the conventional echocardiography, changes in the pulmonary artery / aorta ratio, myocardial performance index, and right ventricular systolic time were observed in both groups, being of lower severity in the treated group. In the two-dimensional Feature tracking mode, the reduction in the rate of right ventricular myocardial deformation in the placebo group was observed (St global: GP 17.37 ± 2.87 and GT 23.71 ± 7.87 – p= 0,0342; overall StR: GP 1.47 ± 0, 28 and GT 2.02 ± 0.69 – p=0,0364). Cerebral natriuretic peptide concentration did not differ between groups. The concentration of nitric oxide was significantly higher in the group treated at 30 and 60 days. The histopathological evaluation showed less pronounced cardiac and pulmonary lesions in the treated group. The data obtained demonstrate the beneficial action of Angiotensin -1-7 in patients with pulmonary hypertension being efficient in the control of cardiac dysfunction and vascular remodeling.