Nitric oxide and vasodilating prostaglandins contribute to the augmented skeletal muscle hyperemia during hypoxic exercise in humans
Crecelius, Anne Renee
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Exercise hyperemia in hypoxia is augmented relative to the same level of exercise in normoxia. At mild exercise intensities, the augmented response is not explained by β-adrenoceptor mediated dilation. We hypothesized that elevated synthesis of nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute to the augmented hyperemic response during hypoxic exercise. To test this hypothesis, in 10 healthy adults, we measured forearm blood flow (FBF; Doppler ultrasound) and calculated the vascular conductance (FVC) responses to rhythmic forearm handgrip exercise (20% maximal voluntary contraction) in normoxia and during systemic isocapnic hypoxia (85% arterial oxygen saturation; pulse oximetry) before and after local intra-brachial combined blockade of nitric oxide synthase (NOS; via NG-monomethyl-ʟ-arginine: ʟ -NMMA) and cyclooxygenase (COX; via ketorolac) inhibition. All trials were performed during local blockade of α- and β-adrenoceptors to eliminate the sympathoadrenal effects on the forearm vasculature and isolate local vasodilation. A deep venous catheter was also placed in the experimental arm. Blood samples were taken from both the arterial and venous catheters and analyzed to assess oxygen extraction and oxygen consumption of the exercising tissue. In control (saline) conditions, FBF after 5 minutes of exercise in hypoxia was greater than in normoxia (345 ± 21 ml min-1 vs 297 ± 18 ml min-1; P<0.05). After NO/PG block, exercise hyperemia was significantly reduced in hypoxia (312 ± 19 ml min-1; P<0.05), but not in normoxia (289 ± 15 ml min-1; P=NS). The observed reduction in FBF during hypoxic exercise after NO/PG block resulted in a significant decrease in oxygen delivery (62 ± 5 ml min-1 vs 56 ± 4 ml min-1; P<0.05). A compensatory increase in extraction was measured (59 ± 3% vs 64 ± 3%; P<0.05) which maintained oxygen consumption (36 ± 3 ml min-1 vs 36 ± 2 ml min-1; P<0.05). We conclude that under the experimental conditions employed, NO and PGs have little role in normoxic exercise hyperemia whereas they significantly contribute to hypoxic exercise hyperemia at this intensity of exercise. The augmented response to hypoxia as compared to normoxia is reduced ~50% with combined NO/PG block. Additionally, during hypoxic exercise after combined NO/PG block, despite a decrease in oxygen delivery driven by attenuated blood flow, muscle oxygen extraction increases to maintain oxygen consumption. The factors contributing to the remaining augmentation of hypoxic exercise hyperemia (~50%) are yet to be determined.