Caracterização parcial do mecanismo cardioprotetor de um tripeptídeo derivado de Ts14, peptídeo vasodilatador da peçonha do escorpião Tityus serrulatus

Abstract

Introduction: The Hypotensin (Ts14) is a vasoactive peptide that is found in the venom of the yellow scorpion Tityus serrulatus. A Ts14-derived synthetic tripeptide can potentiate the hypotensive effect of Bradykinin (BK) and activates the B2 receptor, leading to vasodilation. This tripeptide promotes an anti-hypertensive action in spontaneously hypertensive rats (SHR lineage). When hypertension is not treated, atherosclerosis and myocardial infarction can occur and can progress to heart failure and death. The current treatment for acute myocardial infarction (AMI), which is an ischemic injury of cardiac myocytes, is coronary reperfusion, but reperfusion can also lead to tissue damage. Thus, searching for new cardioprotective agents is in great need. In this regard, preliminary results suggest that this tripeptide induces a positive inotropic effect, due to increased left ventricle developed pressure (LVDP), and reduced heart rate. It also reduced the cardiac arrhythmias associated with I/R. All effects were independent of NO production, which is a common mode of action for cardioprotection. Objective: To characterize the cardioprotective mechanism of the tripeptide in reperfused hearts after experimental I/R. Materials and Methods: Three experimental protocols were organized with male rats: in experimental protocol I, Wistar rats were used, in experimental protocol II, spontaneously hypertensive rats (SHR), and in experimental protocol III, normotensive Sprague Dawley (SD) rats were used. Each of the protocols was divided into 3 experimental groups. The first group consisted of healthy hearts, without I/R induction, while I/R was induced for the second and third groups. The main difference between these last two groups was that the third group was treated with tripeptide before I/R. The experiments were carried out on the Langendorff System and the Krebs-Ringer solution was used for cardiac perfusion. In protocols I and II, preconditioning with the tripeptide (group 3) had a stabilization period of 50 minutes, followed by 30 minutes of ischemia and 30 minutes of reperfusion. The tripeptide perfused the hearts from 20 minutes of the stabilization until the end of reperfusion. In protocol III, preconditioning with the tripeptide (group 3) had a stabilization period of 35 minutes, followed by 25 minutes of ischemia and 60 minutes of reperfusion. The tripeptide perfused the hearts from 20 minutes of the stabilization until the end of reperfusion. Data acquisition was performed using the LabChart program and the region corresponding to the per-ischemic of the hearts was reserved for molecular analysis (Western blotting). The experiments were approved by the local Animal Ethical Commitee (CEUA, Protocol No. 213/2016). Results: evaluated cardiac physiological parameters such as heart rate, maximum and minimum pressures are still not conclusive and it will be necessary to repeat and reassess them. However, tripeptide was shown to increase Akt phosphorylation in treated hearts. Phosphorylated Akt is related to cell survival. Conclusion: This project allowed the partial characterization of the tripeptide cardioprotection mechanism.