Eficácia de novas moléculas anti-hipertensivas com alvo no sistema purinérgico em modelos pré-clínicos: uma revisão sistemática com meta-análise

Abstract

Hypertension (HTN), a chronic disease characterized as an elevated blood pressure condition, has a high prevalence in the world and is responsible for millions of deaths and complications every year. Purinergic signalling plays an important role throughout hypertension mechanisms once purinergic receptors and enzymes act synergically to maintain a physiological blood pressure and vascular integrity. Under increased blood pressure conditions, there is a disturbance in purinergic signalling mediated by adenosine triphosphate (ATP) and its metabolites, in expression or activity of extracellular purinergic enzymes and in activation of P2 and P1 receptors. In this review, we selected 12 studies to analyze the effectiveness of new antihypertensive molecules targeted in purinergic signalling in preclinical models. We searched the following electronic bibliographic databases: MEDLINE via PubMed, Scopus and Embase. The quality of the studies included was analyzed by the SYRCLE's risk of bias tool. The data were meta-analyzed through funnel plot and forest plot. According to the qualitative analysis and meta-analysis all molecules low blood pressure significantly, what was demonstrated through the size of the effect. However, due to molecular mechanisms, route of administration and study quality, AF-219 (P2X3 antagonist), INS45973 (P2Y2 agonist) and Brilliant blue G (BBG; P2X7 antagonist) molecules have a greater therapeutic potential. These results suggest a possible future clinical trial.