Via de sinalização L-arginina/NO/GMPc como alvo do tratamento da embolia pulmonar: uma revisão bibliográfica

Abstract

Pulmonary embolism (PE) is characterized by its high prevalence and mortality. Its treatment aims the clinical and hemodynamic stability and it is restricted mainly to the mechanical obstruction of the thrombus. Studies have shown the relevance of pulmonary arterial vasoconstriction immediately after the onset of PE. As a result, the use of vasodilators becomes a therapeutic possibility for PE. This study aimed to perform a review on the drugs that act on the L-arginine/NO/cGMP pathway for the treatment of PE; hence, we carried out an exploratory integrative review. Therapies found included drugs that increase the bioavailability of L-arginine, phosphodiesterase 5 inhibitor (iPDE5) alone or in combination, soluble guanylate cyclase (GCs) stimulators, antioxidant and inhaled NO (iNO). Among the studies related to the topic, agents that increase the bioavailability of L-arginine (exogenous L-arginine or arginase inhibitor), iPDE5 alone (sildenafil) or in combination (L-arginine, nitrite, NO donor, iNOS inhibitor), GCs stimulators (BAY 41-8543; BAY 41-2272), antioxidant (TEMPOL) and iNO presented favorable results in experimental models, reducing EPA-induced pulmonary arterial hypertension, of which sildenafil showed better results. Inhaled NO was the only drug used in clinical studies. Further investments in large controlled clinical trials should be done in order to establish the optimal dose, the therapeutic range and possible side effects for the treatment of EP with activators of Larginine/NO/GMPc pathaway. The activation of the L-arginine/NO/cGMP pathway is a promising therapeutic target for the treatment of PE.