Avaliação da atividade de peptídeos natriuréticos na angiogênese em modelo de implante de esponja

Abstract

Natriuretic peptides (NPs), endogenous bioactive peptides, modulate endothelial cell functions, besides their well known effects controlling salt, water and blood pressure homeostasis. To date, the effects of NPs on inflammation and angiogenesis are rather contradictory. In this study we evaluated the effects of these peptides on inflammatory angiogenesis induced by polyether polyurethane sponge implants in mice. The hemoglobin content (g/mg wet tissue) and blood flow measurements (laser Doppler perfusion imaging) of the implants used as an index of vascularization showed that single dose of C-ANP4-23, (a ligand for the natriuretic peptide clearance receptor) but not of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) or C-type natriuretic peptide (CNP) reduced angiogenesis in the implants relative to the PBS-treated group, but failed to modulate inflammation in our system. Histological analysis corroborated the biochemical and functional parameters indicative of inhibition of neovascularization. The decreased vascularization of the implants by the peptide was associated with attenuated production of nitric oxide (nitrite levels) and enhanced levels of VEGF. The inhibitory effect of C-ANP4-23 on the angiogenic component of the fibrovascular tissue induced the synthetic matrix extends the range of actions of the peptide and may indicate its therapeutic potential in controlling angiogenesis in fibroproliferative diseases.