Avaliação dos Peptídeos Potenciadores de Bradicinina (BPPs) da Bothrops jararaca na modulação do óxido nítrico e vias hipertróficas em cardiomiócitos.

Abstract

The bradykinin potentiating peptides (BPPs) present in the venon of Bothrops jararaca were the first natural inhibitors described for the angiotensin converting enzyme (ACE). This inhibitory effect seems to explain the strong anti-hypertensive actions of these peptides; however, recently studies suggest that the activity of BPPs is not only related to the inhibition of ACE but may also involve other mechanisms. Therefore, the aim of this work was to evaluate the effects of BPPs on the production of nitric oxide and on hypertrophic signaling in cardiomyocytes. Our results show that BPP-10c and BPP-5a promoted an increase on nitric oxide production in cardiomyocytes isolated from wild type mice and also isolated from Bradykinin B1 and B2 receptor knockout mice. We analyzed the phosphorylation levels of proteins involved on the nitric oxide pathway, p-AKT and p-eNOS, and observed an increase on p-eNOS levels in cardiomyocytes treated with BPP-10c, suggesting an involvement of this enzyme in the nitric oxide production. We also observed that BPP-10c and BPP-5a were able to inhibit the nuclear translocation of GRK5 induced by isoproterenol and phenylephrine and therefore prevented the cellular hypertrophy. Moreover, the anti-hypertrophic effect of BPP-5a was dependent on nitric oxide production. On our in vivo experiments, we evaluated the effects of the BPP-10c infusion on the cardiovascular function and cardiac hypertrophy of wistar rats treated with isoproterenol for seven consecutive days. We observed that concomitant treatment with BPP-10c did not promote any significant alterations on the cardiovascular function of isoproterenol treated rats, however, prevented the cardiac hypertrophy induced by isoproterenol. Taken together, these findings suggested that BPPs are important cardioprotectors opening new perspectives for the development of drugs based on BPPs.