An orally active angiotensin-(1-7) inclusion compound and exercise training produce similar cardiovascular effects in spontaneously hypertensive rats.

Low angiotensin-(1-7) (Ang-(1-7)) concentration is observed in some cardiovascular diseases and exercise training seems to restore its concentration in the heart. Recently, a novel formulation of an orally active Ang-(1-7) included in hydroxy-propyl-beta-cyclodextrin (HPB-CD) was developed and chronically administered in experimental models of cardiovascular diseases. The present study examined whether chronic administration of HPB-CD/Ang-(1-7) produces beneficial cardiovascular effects in spontaneously hypertensive rats (SHR), as well as to compare the results obtained with those produced by exercise training. Male SHR (15-week old) were divided in control (tap water) or treated with HPB-CD/Ang-(1-7) (corresponding to 30µgkg(-1)day(-1) of Ang-(1-7)) by gavage, concomitantly or not to exercise training (treadmill, 10 weeks). After chronic treatment, hemodynamic, morphometric and molecular analysis in the heart were performed. Chronic HPB-CD/Ang-(1-7) decreased arterial blood pressure (BP) and heart rate 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 in SHR. Chronic treatment improved autonomic control by attenuating sympathetic modulation on heart and 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 chronic treatment with the HPB-CD/Ang-(1-7) inclusion compound produced beneficial effects in SHR resembling the ones produced by exercise training. This observation reinforces the potential cardiovascular therapeutic effect of this novel peptide formulation.

A novel approach based on nanotechnology for investigating the chronic actions of short-lived peptides in specific sites of the brain.

This review presents a novel experimental approach for investigating the chronic actions of short-lived peptides in specific sites of the brain. This method combines the advantages of three different techniques: liposome encapsulation, site-specific microinjection and telemetry. First, liposomes can be designed to remain located at the injection site for a long period of time, where they protect encapsulated peptide from rapid degradation and act as a sustained-release system. Secondly, microinjection allows the administration of peptides in specific sites of the brain with minimal side effects. Finally, using telemetry, it is possible to register physiological parameters and their circadian variations in undisturbed free-moving animals for several days. Angiotensin-(1-7) and angiotensin II were used as peptide models, in order to validate the proposed method. Following the unilateral microinjection of the liposome-encapsulated peptides into the rostral ventrolateral medulla (RVLM) of Wistar rats, long-lasting cardiovascular actions were elicited, for several days. Importantly, new physiological actions of angiotensin-(1-7) at the RVLM were unmasked: modulation of the circadian rhythms of blood pressure and heart rate. It is felt that this method can be applied to a wide variety of short-lived bioactive peptides and should encounter numerous applications in the field of neurosciences.