Long-lasting cardiovascular effects of liposome-entrapped angiotensin-(1-7) at the rostral ventrolateral medulla

Abstract

The aim of this work was to evaluate the potential of liposomes as a tool for the sustained release of the short half-life peptides of the renin-angiotensin system in a specific site of the brain. Angiotensin (Ang)-(1-7) was selected for this study because of its known cardiovascular effects at the level of the rostral ventrolateral medulla (RVLM) and because of the considerable interests in elucidating its physiopathological role as a neuromodulator. Ang-(1-7)-containing liposomes (LAng) were microinjected unilaterally in the RVLM of Wistar rats, and the effects on blood pressure (MAP) and heart rate were evaluated by telemetry. Empty liposomes (Lemp) were used as control. LAng elicited a significant pressor effect during daytime and bradycardia during nighttime that lasted for 5 and 3 days, respectively. These cardiovascular effects resulted in a significant attenuation of the circadian variations of MAP and heart rate. In the case of MAP, a significant inversion of the circadian rhythm was observed on day 2 after LAng microinjection. None of these effects were observed following microinjection of Lemp. Using this novel technique, it was possible to establish, in chronic conditions, the pressor effect of Ang-(1-7) at the RVLM. Moreover, our data unmasks a new physiological role for Ang-(1-7) at the level of the RVLM: modulation of the circadian rhythms of MAP and heart rate.