Avaliação de efeitos cardiovasculares da angiotensina (1-7) após administração do peptídeo em formulação oral em felinos

Abstract

Therapeutic strategies aimed at cardioprotection are the target of intense studies to reduce the progression of cardiovascular diseases, as well as associated clinical signs. Especially for cats, the hypertrophic cardiomyopathy (HCM) phenotype is currently the main feline cardiovascular disease, characterized by ventricular hypertrophy, with variable clinical signs depending on the stage of the disease. One of the treatment strategies that have cardioprotective potential that may be applicable to cats is the use of peptides from the renin angiotensin system (RAS), especially angiotensin 1-7. Ang-(1- 7) is a heptapeptide, derived from angiotensin II or angiotensin 1-9, having a cardioprotective effect, with blood pressure control, vasodilatory, antifibrotic, antiremodeling properties, composing the counter-regulatory axis ACE2/Ang-(1-7)/Mas with opposite effects to ECA/Ang II/AT1R. Its use is already the subject of intense research with various animal experimental models, however, its cardioprotective effect has not yet been evaluated in feline species. The objective of the present study was to evaluate the cardiovascular effects of the administration of Ang-(1-7) in an oral formulation for healthy felines. Around 6 felines, males and females, were randomly selected to compose 3 experimental groups (A, B and C) to be subjected to administration of Ang-(1-7) at doses of 30 μg/kg, 60 μg/kg and placebo; all animals were subjected to all treatments with a 7-day washout. Clinical, cardiological, blood pressure, electrocardiographic and echocardiographic evaluations were carried out in the baseline, 6, 12, 24h, and 15 days after the end. Two statistical models were applied, comparing doses and times considering all moments (model 1) and only between doses and time (model 2); p-value <0.05. A significant difference was observed for hair filling time in the baseline T6h and treatment 60 μg/kg T6h between multiple comparisons (model 1) and time effect without comparison (model 2); R wave amplitude with difference between dose and time with multiple comparison (model 1); T wave duration and end-diastolic volume (EDV) with dose effect, but without multiple comparison (model 2); dose and time effect with multiple comparison (model 1) and time effect without comparison (model 2) for aortic flow. The two doses used in oral formulation were well tolerated and safe for healthy felines. The dosages used (30 and 60 μg/kg; single administration) were not sufficiently capable of promoting a negative hemodynamic impact in healthy felines, although isolated effects were observed.