Induction of Cardiac Nitric Oxide Synthase 2 in Rats Exposed to Chronic Hypoxia

Induction of nitric oxide synthase (NOS2, also designated as iNOS) in the heart is known to occur in response to various stimuli. It is not known, however, whether in vivo hypoxia leads to cardiac NOS2 induction. We thus investigated the effects of normobaric hypoxia (10% O2for 8, 15 and 21 days) on NOS2 protein expression and enzyme activity in rat right ventricle (RV) and left ventricle (LV). Chronic hypoxia induced RV hypertrophy: the RV weight to body weight ratio was increased by 45% upon 15 days of exposure, with no change thereafter and no change in left ventricular (LV) weight. Treatment of hypoxic rats with l -NAME for 1 month decreased pulmonary artery pressure and RV hypertrophy compared to hypoxic non-treated rats. NOS2 activity detected by [3H]l -arginine to [3H]l -citrulline conversion increased in RV during hypoxia, with a maximum at 15 days (+161% of control rats P