Background Pulmonary arterial hypertension (PAH) is a rare progressive, usually fatal lung disease of different ethiologies. Endothelial cell dysfunction contributes to the pathogenesis, although the specific mechanisms are not clear. Impaired vascular cGMP signaling seems to be involved in the development of pulmonary vascular remodeling and constriction, because drugs preventing cGMP degradation or stimulating cGMP production showed beneficial effects. Atrial (ANP) and B-type natriuretic peptides (BNP) both act through the guanylyl cyclase-A (GC-A) receptor and stimulate cGMP production in all vascular cell types (i.e.endothelial cells (EC), smooth muscle cells (SMC) and fibroblasts). The purpose of the study was to analyze whether mice with global or conditional, ECor SMC-restricted GC-A ablation develop PH under normoxic conditions and which genes are differentially expressed.