An orally active angiotensin-(1–7) inclusion compound and exercisetraining produce similar cardiovascular effects in spontaneouslyhypertensive rats.

Abstract

Low angiotensin-(1–7) (Ang-(1–7)) concentration is observed in some cardiovascular diseases and exer-cise training seems to restore its concentration in the heart. Recently, a novel formulation of an orallyactive Ang-(1–7) included in hydroxy-propyl-beta-cyclodextrin (HPB-CD) was developed and chronicallyadministered in experimental models of cardiovascular diseases. The present study examined whetherchronic administration of HPB-CD/Ang-(1–7) produces beneficial cardiovascular effects in spontaneouslyhypertensive rats (SHR), as well as to compare the results obtained with those produced by exercisetraining. Male SHR (15-week old) were divided in control (tap water) or treated with HPB-CD/Ang-(1–7)(corresponding to 30 _g kg−1day−1of Ang-(1–7)) by gavage, concomitantly or not to exercise training(treadmill, 10 weeks). After chronic treatment, hemodynamic, morphometric and molecular analysis inthe heart were performed. Chronic HPB-CD/Ang-(1–7) decreased arterial blood pressure (BP) and heartrate in SHR. The inclusion compound significantly improved left ventricular (LV) end-diastolic pressure,restored the maximum and minimum derivatives (dP/dT) and decreased cardiac hypertrophy index inSHR. Chronic treatment improved autonomic control by attenuating sympathetic modulation on heartand vessels and the SAP variability, as well as increasing parasympathetic modulation and HR variability.Overall results were similar to those obtained with exercise training. These results show that chronictreatment with the HPB-CD/Ang-(1–7) inclusion compound produced beneficial effects in SHR resem-bling the ones produced by exercise training. This observation reinforces the potential cardiovasculartherapeutic effect of this novel peptide formulation.