Interestingly, PKC-ε −/− mice had a much greater increase in right ventricular (RV) systolic pressure, RV mass, and hematocrit in response to Hx than +/+ mice (n = 9 to 13 mice per group; p < 0.05). Despite the increased pulmonary artery pressure and RV hypertrophy, PKC-ε null mice showed no further pulmonary vascular remodeling compared to controls. The acute inhalation of nitric oxide reversed the increased vascular tone in chronically hypoxic null mice, implying that the exaggerated pulmonary hypertension seen here could be due to a relative deficiency in endothelial nitric oxide synthase (eNOS) expression/activity. Baseline eNOS protein expression was similar in PKC-ε +/+ and −/− lungs. The expected Hx-induced increase in lung eNOS expression was attenuated in PKC-ε null mice.