Abstract 17700: Protective Role of Myelocytic Nitric Oxide Synthases in Hypoxic Pulmonary Hypertension in Mice

Background: All three nitric oxide synthases (nNOS, iNOS, and eNOS) are expressed under pulmonary hypertensive conditions. Although the role of all the NOSs in pulmonary hypertension (PH) has been examined in pharmacological studies with non-selective NOSs inhibitors, obtained results are inconsistent possibly due to non-specificity of the agents. We addressed this point in our mice lacking all the NOSs. Methods and Results: Wild-type (WT), single nNOS-/-, iNOS-/-, eNOS-/-, and triple n/i/eNOSs-/- mice were exposed to hypoxia for 3 weeks. Hypoxic exposure significantly reduced survival rate only in the triple NOSs-/- genotype (P<0.05, n=14-34). Hypoxic exposure increased right ventricular (RV) pressure (RVP), RV hypertrophy (RVH), and medial thickening of small pulmonary arteries (MT) in all the genotypes. Notably, RVP were significantly worsened in the triple NOSs-/- genotype, and, to a lesser extent, in the eNOS-/- genotype, but not in the nNOS-/- or iNOS-/- genotype, as compared with the WT genotype, a...