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

TY - JOUR

T1 - Regulation of bone blood flow in humans

T2 - The role of nitric oxide, prostaglandins, and adenosine

AU - Heinonen, Ilkka

AU - Boushel, Robert

AU - Hellsten, Ylva

AU - Kalliokoski, Kari

N1 - CURIS 2018 NEXS 099

PY - 2018/5

Y1 - 2018/5

N2 - 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 ± 0.4 mL 100 g−1min−1 and increased to almost sixfold in response to exercise (6.3 ± 1.5 mL 100 g−1 min−1). Inhibition of NOS reduced BBF at rest to 0.7 ± 0.3 mL 100 g−1 min−1 (P =.036), but did not affect BBF significantly during exercise (5.5 ± 1.4 mL 100 g−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 ± 0.2 mL 100 g−1min−1), the combined blockade reduced BBF during exercise by ~21%, to 5.0 ± 1.8 mL 100 g−1min−1 (P =.014). Finally, the ADO inhibition during exercise reduced BBF from 5.5 ± 1.9 mL 100 g−1 min−1 to 4.6 ± 1.2 mL 100 g−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.

AB - 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 ± 0.4 mL 100 g−1min−1 and increased to almost sixfold in response to exercise (6.3 ± 1.5 mL 100 g−1 min−1). Inhibition of NOS reduced BBF at rest to 0.7 ± 0.3 mL 100 g−1 min−1 (P =.036), but did not affect BBF significantly during exercise (5.5 ± 1.4 mL 100 g−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 ± 0.2 mL 100 g−1min−1), the combined blockade reduced BBF during exercise by ~21%, to 5.0 ± 1.8 mL 100 g−1min−1 (P =.014). Finally, the ADO inhibition during exercise reduced BBF from 5.5 ± 1.9 mL 100 g−1 min−1 to 4.6 ± 1.2 mL 100 g−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.

KW - Bone

KW - Marrow

KW - Blood flow

KW - Nitric oxide

KW - Prostanoids

KW - Exercise

KW - Humans

U2 - 10.1111/sms.13064

DO - 10.1111/sms.13064

M3 - Journal article

C2 - 29377406

SN - 0905-7188

VL - 28

SP - 1252

EP - 1258

JO - Scandinavian Journal of Medicine & Science in Sports

JF - Scandinavian Journal of Medicine & Science in Sports

IS - 5

ER -