Augmented skeletal muscle hyperaemia during hypoxic exercise in humans is blunted by combined inhibition of nitric oxide and vasodilating prostaglandins

作者：Crecelius Anne R; Kirby Brett S; Voyles Wyatt F; Dinenno Frank A^*

来源：The Journal of Physiology, 2011, 589(14): 3671-3683.

DOI：10.1113/jphysiol.2011.209486

Exercise hyperaemia in hypoxia is augmented relative to the same level of exercise in normoxia. At moderate exercise intensities, the mechanism(s) underlying this augmented response are currently unclear. We tested the hypothesis that endothelium-derived nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute to the augmented muscle blood flow during hypoxic exercise relative to normoxia. In 10 young healthy adults, we measured forearm blood flow (FBF; Doppler ultrasound) and calculated the vascular conductance (FVC) responses during 5 min of rhythmic handgrip exercise at 20% maximal voluntary contraction in normoxia (NormEx) and isocapnic hypoxia (HypEx; O-2 saturation similar to 85%) before and after local intra-brachial combined blockade of NO synthase (NOS; via N-G-monomethyl-L-arginine: L-NMMA) and cyclooxygenase (COX; via ketorolac). All trials were performed during local alpha- and beta-adrenoceptor blockade to eliminate sympathoadrenal influences on vascular tone and thus isolate local vasodilatation. Arterial and deep venous blood gases were measured and oxygen consumption ((V) over dotO(2)) was calculated. In control (saline) conditions, FBF after 5 min 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, the compensatory increase in FBF during hypoxic exercise was blunted similar to 50% and thus was reduced compared with control hypoxic exercise (312 +/- 19 ml min(-1); P < 0.05), but this was not the case in normoxia (289 +/- 15 ml min(-1); P = 0.33). The lower FBF during hypoxic exercise was associated with a compensatory increase in O-2 extraction, and thus (V) over dotO(2) was maintained at normal control levels (P = 0.64-0.99). We conclude that under the experimental conditions employed, NO and PGs have little role in normoxic exercise hyperaemia whereas combined NO-PG inhibition reduces hypoxic exercise hyperaemia and abolishes hypoxic vasodilatation at rest. Additionally, (V) over dotO(2) of the tissue was maintained in hypoxic conditions at rest and during exercise, despite attenuated oxygen delivery following NO-PG blockade, due to an increase in O-2 extraction at the level of the muscle.

• 出版日期2011-7-15