RATIONALE: Physiological responses to hypoxia involve adaptations in the hematopoietic and cardiovascular systems, which work together to ensure adequate oxygen delivery to tissues for energy production. The arginine/nitric oxide (NO) pathway regulates both systems through its effects on erythropoiesis and vasodilation. In Tibetan populations native to high-altitude hypoxia, increased NO production from arginine and decreased arginine metabolism by arginase contribute to these adaptive mechanisms. These metabolic changes enhance tissue oxygen delivery and reduce the risk of hypoxic pulmonary hypertension. Here, we hypothesize that genetic deletion of mitochondrial arginase 2 ( METHODS: Complete blood counts, bone marrow erythroid differentiation, plasma arginine and NO (measured as nitrite), right ventricular systolic pressure (RVSP), heart rate, heart weight, and blood pressure were measured in wild-type (WT) and RESULTS: Under normoxic conditions, CONCLUSIONS: Arginine metabolism in the mitochondria plays a key role in modulating adaptive responses to hypoxia. Deletion of