Abstract: AIM To investigate the in vivo effects of AC-NP on hypoxia-induced pulmonary hypertension (HPH). AC-NP is a novel 28-amino acid chimeric peptide, which combines the 17-amino acid ring of C type natriuretic peptide (CNP) with 6-amino acid N-terminus and 5-amino acid C-terminus of atrial natriuretic peptide (ANP). METHODS The HPH model was developed by subjecting rats to hypobaric hypoxia. HPH rats were then treated with either VNP (50 μg/kg per day, i.p.) or saline (0.5 ml, i.p.) every day for 7 days. Hemodynamic indices, right ventricular hypertrophy (RVH) and remodeling of the pulmonary arteries were evaluated. RESULTS Hypobaric hypoxia induced severe HPH compared with that in normoxic control group. Treatment of HPH rats with VNP for 1 week significantly reduced mean pulmonary arterial pressure, pulmonary vascular resistance, RVH and muscularization of the pulmonary arteries, although pulmonary blood flow was increased in this group. In addition, acute i.v. administration of AC-NP significantly ameliorated pulmonary haemodynamics in HPH rats. CONCLUSION SAC-NP has certain therapeutic effects against HPH.