Long-Lasting Pressor Effect of Liposome-Encapsulated Angiotensin-(1-7) Following Unilateral Microinjection into the Rat Rostral Ventrolateral Medulla
Several studies with vasoactive peptides in the rostral ventrolateral medulla (RVLM) have focused on their acute cardiovascular effects. However, information is still lacking on their long term effects in this key region for the central control of blood pressure. Sterically stabilized liposomes (SSL) represent an important tool for the slow release of bioative agents and the prolongation of their effect in vivo. In this work, we administered Angiotensin(Ang)-(1-7)-containing SSL in the RVLM and evaluated its effects on blood pressure (BP) and heart rate (HR). Ang-(1-7) was encapsulated in SSL made from disteroylphosphatidylcholine, cholesterol and polyethyleneglycol-phosphatidylethanolamine (PEG-2000PE) at a molar ratio of 5:4:0.3. Peptide-containing liposomes were separated from unencapsulated peptide by dialysis and then sterilized by filtration. The final preparation showed a mean vesicle diameter of 0,2 μm and a weight ratio of encapsulated peptide to lipid of 0.03 (w/w). Ang-(1-7)-containing liposomes (36 ng peptide/200 nl) and empty lipossomes (control) were unilaterally microinjected in the RVLM of Wistar rats. The effects on BP and HR in freely-moving rats were evaluated by telemetry. The group microinjected with SSL-Ang-(1-7) exhibited a significant increase in mean arterial blood pressure (MAP) that was maintained for 4 days (MAP = 112 ± 2.3 mmHg vs 97 ± 2.0 mmHg, p<0.05). On the other hand, the microinjection of empty liposomes did not produced any significant alteration of BP. Strikingly, the normal circadian variations of the BP and HR were markedly attenuated in SSL-Ang-(1-7) group only. In conclusion, the site specific (RVLM) microinjection of SSL-Ang-(1-7) produced a long-lasting pressor effect. Furthermore, these data unmasked a new physiological role for Ang-(1-7) at the level of RVLM: modulation of circadian rhythm of BP.