AVALIAÇÃO DO ENVOLVIMENTO DOS RECEPTORES B1 E B2 PARA CININAS EM ALTERAÇÕES INFLAMATÓRIAS E CARDIOVASCULARES SISTÊMICAS INDUZIDAS PELA PERIODONTITE

Abstract

The inflammatory process is associated with increased plasma levels of bradykinin (BK) and its metabolites des-Arg9-bradykinin (DABK) and des-Arg10-lys-bradykinin. The kinins effects are mediated through B1 and B2 receptors activation. BK acts preferentially in the constitutive B2 receptors. In contrast, BK metabolites act in the B1 receptors that are expressed only in tissues that have undergone previous trauma or infection. Studies suggest that the action of the B1 receptor is correlated to chronic inflammatory processes such as periodontitis. Thus, the purpose of this study was to investigate the involvement of B1 and B2 kinin receptors in systemic inflammation and cardiovascular changes induced by periodontitis in rats. Fourteen days after the induction of periodontitis by ligature placement or sham procedure, animals were underwent to the paw edema procedure induced for different phogistic agents – carragenan, BK, DABK, serotonin and prostaglandin E2. In addition to the paw edema procedure the migration of polymorphonuclear cells and vascular permeability changes were evaluated after carrageenan-induced paw edema. In the same period of time the assessment of changes in mean arterial pressure for B1 and B2 receptors agonists were determinate. The plasma and tissue levels (paw tissue) of TNF-α and IL-1β were quantified after three, seven and fourteen days of periodontitis induction. The protein quantification (western-blotting) of B1 receptor was determinate after fourteen days of periodontitis induction. The results obtained for paw edema procedure mediated by carrageenan demonstrated a statistically significant increase in the edema, polymorphonuclear cells migration and vascular permeability in the ligature group. No differences between the ligature and sham group were observed in paw edema induced by serotonin, histamine and prostaglandin E2. No differences between the ligature and sham group were observed in BK-induced paw edema. Interestingly, the DABK-induced paw edema was increased at ligature group. Therefore the increase at edema induced by DABK-indicate the activation of the B1 receptors in the paw edema in ligature group, but changes in protein quantification of B1 receptor were not observed between experimental groups. The changes in blood pressure induced by BK and DABK agonist were similar. The plasma levels of TNF-α were higher in the ligature group after three days of periodontitis induction. In contrast, tissue levels of IL-1β were higher in the ligature group. The data suggest that periodontitis can promote changes in inflammatory response in tissues distant from oral cavity. Thus, alterations in inflammatory parameters can increase the expression of B1 receptors, and these receptors may contribute in the systemic inflammatory changes induced by periodontitis.