Madery, Brandon D.

We previously reported that augmented skeletal muscle vasodilation during mild hypoxic forearm exercise includes beta‐adrenergic mechanisms. Furthermore, hypoxic vasodilation at rest is known to include beta‐adrenergic mediated nitric oxide (NO) production. Therefore, we tested the hypothesis that NO contributes to augmented vasodilation with hypoxic exercise. Twelve subjects (6M/6F; 26 ± 2 years) breathed hypoxic gas to titrate arterial O 2 saturation to 80% while remaining normocapnic via a rebreath system. Subjects performed incremental forearm exercise (10% and 20% of maximum) during saline infusion (control) and NO synthase inhibition ( N G ‐monomethyl‐L‐arginine; L‐NMMA) under normoxic and hypoxic conditions. Forearm vascular conductance (FVC; ml/min/100mmHg) was calculated from blood flow (ml/min) and blood pressure (mmHg). During the control condition, the rise in FVC (Δfrom normoxic baseline) due to hypoxic exercise was 211 ± 23 and 367 ± 34 (10% and 20% respectively). Infusion of L‐NMMA during hypoxic exercise attenuated ΔFVC at 10% (174 ± 20; P < 0.001) and 20% (317 ± 32; P < 0.01) compared to control condition. Our data indicate that NO contributes to the augmented vasodilation observed during hypoxic exercise. Supported by NIH HL‐46493 (MJJ) and AR‐55819 (DPC) and by CTSA RR‐024150.

We tested the hypothesis that adenosine contributes to augmented skeletal muscle vasodilation during hypoxic exercise. In separate protocols, subjects performed incremental rhythmic forearm exercise (10% and 20% of maximum) during normoxia and normocapnic hypoxia (80% arterial O2saturation). In protocol 1 ( n = 8), subjects received an intra-arterial administration of saline (control) and aminophylline (adenosine receptor antagonist). In protocol 2 ( n = 10), subjects received intra-arterial phentolamine (α-adrenoceptor antagonist) and combined phentolamine and aminophylline administration. Forearm vascular conductance (FVC; in ml·min−1·100 mmHg−1) was calculated from forearm blood flow (in ml/min) and blood pressure (in mmHg). In protocol 1, the change in FVC (ΔFVC; change from normoxic baseline) during hypoxic exercise with saline was 172 ± 29 and 314 ± 34 ml·min−1·100 mmHg−1(10% and 20%, respectively). Aminophylline administration did not affect ΔFVC during hypoxic exercise at 10% (190 ± 29 ml·min−1·100 mmHg−1, P = 0.4) or 20% (287 ± 48 ml·min−1·100 mmHg−1, P = 0.3). In protocol 2, ΔFVC due to hypoxic exercise with phentolamine infusion was 313 ± 30 and 453 ± 41 ml·min−1·100 mmHg−1(10% and 20% respectively). ΔFVC was similar at 10% (352 ± 39 ml·min−1·100 mmHg−1, P = 0.8) and 20% (528 ± 45 ml·min−1·100 mmHg−1, P = 0.2) hypoxic exercise with combined phentolamine and aminophylline. In contrast, ΔFVC to exogenous adenosine was reduced by aminophylline administration in both protocols ( P < 0.05 for both). These observations suggest that adenosine receptor activation is not obligatory for the augmented hyperemia during hypoxic exercise in humans.