T Ago35a.p65

Mailing address: Antonio Augusto Lopes – InCor Cardiologia Pediátrica e Cardiopatias Congênitas do Adulto Av. Dr. Eneas de Carvalho Aguiar, 44 05403-000 São Paulo, SP E-mail: [email protected] Sent for publishing on 03/02/2005 Accepted on 04/04/2005 In the last decades there has been a growing interest for the understanding of pathophysiological mechanisms of pulmonary hypertension, especially in pulmonary arterial hypertension (PAH). Progresses have been more evident concerning the so-called idiopathic PAH (sporadic and familial, previously called primary pulmonary hypertension). Genes were identified whose changes may be related to the disease unleashing (bone morphogenetic protein type 2 receptor, BMPR2). Other genes have been identified as facilitators (serotonin transporter). Besides, from studies in animal models and cellular culture, a series of biological changes have been identified. Such changes involve endothelial cells, smooth muscle cells, fibroblasts, extracellular matrix, pericellular proteolysis, growth factors and their receptors, among others. The present review aims at identifying the main pathophysiological changes known at PAH so far. Besides, two PAH families are shown with the objective of emphasizing the importance of genetic diagnosis and draw the attention to signaling pathways (nitric oxide/cyclic GMP), currently used in therapeutic interventions (sildenafil, chronic use).