Regulation of bone blood flow in humans: The role of nitric oxide, prostaglandins, and adenosine.

Abstract

The mechanisms that regulate bone blood flow (BBF) in humans are largely unknown. Animal studies suggest that nitric oxide (NO) could be involved, and in this study, we investigated the effects of inhibition of nitric oxide synthase (NOS) alone and in combination with inhibition of cyclooxygenase (COX) enzyme, thus prostaglandin (PG) synthesis on femoral bone marrow blood flow by positron emission tomography in healthy young men at rest and during one-leg dynamic exercise. In an additional group of healthy men, the role of adenosine (ADO) in the regulation of BBF during exercise was investigated by use of an adenosine receptor blocker (aminophylline). Inhibitors were directly infused into the femoral artery. Resting BBF was 1.1±0.4mL100g-1 min-1 and increased to almost sixfold in response to exercise (6.3±1.5mL100g-1 min-1 ). Inhibition of NOS reduced BBF at rest to 0.7±0.3mL100g-1 min-1 (P=.036), but did not affect BBF significantly during exercise (5.5±1.4mL100g-1 min-1 , P=.25). On the other hand, while combined NOS and COX inhibition did not cause any further reduction of blood flow at rest (0.6±0.2mL100g-1 min-1 ), the combined blockade reduced BBF during exercise by ~21%, to 5.0±1.8mL100g-1 min-1 (P=.014). Finally, the ADO inhibition during exercise reduced BBF from 5.5±1.9mL100g-1 min-1 to 4.6±1.2mL100g-1 min-1 (P=.045). In conclusion, our results support the view that NO is involved in controlling bone marrow blood flow at rest, and NO, PG, and ADO play important roles in controlling human BBF during exercise.