Compensatory vasodilatation during hypoxic exercise: mechanisms responsible for matching oxygen supply to demand

Abstract

Hypoxia can have profound influences on the circulation. In humans, acute exposure to moderate hypoxia has been demonstrated to result in vasodilatation in the coronary, cerebral, splanchnic and skeletal muscle vascular beds. The combination of submaximal exercise and hypoxia produces a 'compensatory' vasodilatation and augmented blood flow in contracting skeletal muscles relative to the same level of exercise under normoxic conditions. This augmented vasodilatation exceeds that predicted by a simple sum of the individual dilator responses to hypoxia alone and normoxic exercise. Additionally, this enhanced hypoxic exercise hyperaemia is proportional to the hypoxia-induced fall in arterial oxygen (O(2)) content, thus preserving muscle O(2) delivery and ensuring it is matched to demand. Several vasodilator pathways have been proposed and examined as likely regulators of skeletal muscle blood flow in response to changes in arterial O(2) content. The purpose of this review is to put into context the present evidence regarding mechanisms responsible for the compensatory vasodilatation observed during hypoxic exercise in humans. Along these lines, this review will highlight the interactions between various local metabolic and endothelial derived substances that influence vascular tone during hypoxic exercise.

Figure 1. Matching blood flow to metabolism during exercise

One-legged blood flow during incremental knee-extensor exercise and incremental and supramaximal cycling to exhaustion plotted against one-legged V_O2. Adapted with permission from Mortensen et al. (2008).

Figure 2. Hypoxia induced increases in muscle sympathetic nerve activity (MSNA)

Representative recordings of leg MSNA at rest and during exercise under normoxia ( 21%; A) and hypoxia () ∼10%; B). Adapted with permission from Hanada et al. (2003).

Figure 3. Proposed mechanisms for hypoxia-induced vasodilatation at rest and during exercise

During hypoxic exercise NO is the final common pathway for the compensatory dilator response. Systemic adrenaline release, acting via β-adrenergic receptors, contributes to the NO-mediated vasodilatation at lower exercise intensities, but this β-adrenergic contribution decreases with increasing exercise intensity. ATP released from the red blood cell remains an attractive candidate for stimulating NO during higher intensity hypoxic exercise. Adenosine receptor activation does not appear to play a major role (either dependent or independent of NO) in the compensatory vasodilator response during hypoxic exercise in humans. Compensatory vasodilatation persists despite an increased sympathetic vasoconstrictor activity directed towards skeletal muscle during hypoxic exercise. Blunted vasoconstrictor responsiveness (augmented functional sympatholysis) does not appear to contribute to the compensatory vasodilatation during hypoxic exercise. α₁ and α₂ indicate α₁ and α₂ adrenergic receptors, respectively; A1 and A2, adenosine receptors; β, β₂ adrenergic receptors; Adr, adrenaline.