AIM:To investigate the roles of nitric oxide (NO) and endothelin-1(ET-1) in regulation of coronary vascular reserve (CVR) during hypoxia.METHODS: CVR were measured with 99m TC radiolabelled frog RBC, the changes of NO - 2,ET-1 contents, nitric oxide synthase(NOS) activity and the myocardial morphometry were observed. RESULTS: (1) Acute hypoxia caused an increase in left and right ventricular myocardial blood flow,myocardial NO - 2,ET-1 contents,NOS activity,but CVR in the left and right ventricle were decreased compared with the control group.(2) Intermittent hypobaric hypoxia for 90 days did not lead to significant change in left ventricular CVR,myocardial ET-1/NO - 2 ratio. However, right ventricular myocardial ET-1 contents,ET-1/ NO - 2 ratio were increased,right ventricular CVR and myocardial NO - 2 contents were decreased. We also observed that perivascular collagen,arterial wall thickness in right ventricle, hematocrit,RV weight index were augmented. CONCLUSION: Rest myocardial blood flow was increased,CVR was decreased;The decreased coronary vascular reserve during chronic hypoxia might be resulted from the increased hematocrit,arterial wall thickness,perivascular collagen,ET-1 content, the decreased NO content and right ventricular hypertrophy.