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(Hypertension. 2001;38:1266.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Long-Lasting Cardiovascular Effects of Liposome-Entrapped Angiotensin-(1-7) at the Rostral Ventrolateral Medulla

Neila M. Silva-Barcellos; Frédéric Frézard; Sordaini Caligiorne; Robson A.S. Santos

From the Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Dr Silva-Barcellos’ permanent address is the Departamento de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.

Correspondence to Robson A.S. Santos, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil. E-mail marrob{at}dedalus.lcc.ufmg.br

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.

Key Words: liposomes • angiotensin-(1-7) • cardiovascular effects • rostral ventrolateral medulla • Blood pressure • heart rate

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