Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), cardiac hormones showing similarity in biological actions and amino acid sequence, are synthesized and secreted by atrial and ventricular tissue during pulmonary vascular remodelling. In the isolated and perfused rat lung preparation ANP and BNP are equipotent in attenuating hypoxic pulmonary vasoconstriction (HPV) in the normal and the remodelled circulation. Synthesis and secretion of ANP is increased in pulmonary vascular remodelling, plasma levels showing a 170%-240% increment whether the experimental model used is chronic hypoxia or monocrotaline. The right ventricle, a site of constitutive synthesis of ANP, shows greater than ten- fold increase in immunoreactive ANP and a 160-fold increase in ANPmRNA suggesting that ventricular synthesis predominates during the processes of ventricular hypertrophy. Despite sustained raised levels of ANP throughout remodelling, vascular responses to ANP and BNP assessed in the intact animal, the isolated perfused lung, or in small pulmonary arteries, are all maintained or increased. A body of research has shown a role of natriuretic peptides on vascular smooth muscle hypertrophy and proliferation during the development of vascular remodelling. In the rat model of chronic hypoxia, studies of continuous infusion of synthetic ANP have shown that ANP exerts an antiproliferative action on the vascular smooth muscle during pulmonary remodelling. Inhibition of neutral endopeptidase 24.11, the major enzymatic pathway of ANP degradation by the specific inhibitor UK 73,967 (candoxatrilat, Pfizer) has suggested that endogenous ANP can attenuate remodelling and cardiac hypertrophy, thus raising therapeutic possibilities. ANP displays an antiproliferative and antihypertrophic effect on vascular smooth muscle cells in in vitro experiments, when stimulated by platelet derived growth factor-B (PDGF-B), effects that are mimicked by 8-bromo- cyclic-guanosine mono phosphate.