Do muscle blood flow detectors link breathing to oxygen consumption in exercise?

Abstract

One of the mysteries of physiology is how breathing is so closely linked to oxygen consumption in a wide variety of conditions such that arterial PO2 and PCO2 remain constant. This is especially true in mild to moderate aerobic muscular exercise where alveolar ventilation increases in direct proportion to oxygen consumption. How this occurs has been difficult to understand. There are two schools of thought. (1) ‘Central command’. The brain ‘decides’ to exercise and matches the motor activities of locomotion and breathing. This view arises from the observation that stimulation of specific brain regions increases both locomotor activity and breathing in a coordinated manner (Eldridge et al. 1985). The mystery here is how these neural events can be linked to metabolism in the distant tissue. (2) ‘Peripheral signals.’ Receptors in the periphery detect oxygen utilization (or its corollaries) and report to the brain, which then modifies breathing. Eligible receptors include the carotid body and the central chemoreceptors, which are quite sensitive to small changes in CO2, and an array of receptors in muscle that respond to mechanical and/or chemical signals including ATP (Kaufman & Hayes, 2002; Hanna & Kaufman, 2003). Haouzi and colleagues have been pursuing a particularly interesting subset of the ‘peripheral signals’ hypothesis, that sensory afferents detect the distension of small blood vessels (Haouzi et al. 2004). This distension could reflect muscle blood flow, which changes in proportion to tissue oxygen utilization. In this issue of The Journal of Physiology, Haouzi & Chenuel (2005) provide data that rule out any role for the carotid body and the central chemoreceptors in the exercise breathing response and indirectly support the vessel distension (blood flow) hypothesis. The experimental model is an anaesthetized sheep with exercise produced by electrically induced rhythmic muscle contractions (ERC). The induction of exercise by ERC eliminates ‘central command’ as a variable. By clever use of the vagaries of the cerebral circulation in this species, they perfuse vessels supplying both the carotid body and the central chemoreceptors with blood of constant arterial PO2 and PCO2 eliminating them as a source of the signal to breathe. During ERC under these conditions, ventilation still increases in direct proportion to muscle oxygen utilization. With block of venous return the appropriate match of ventilation to oxygen use remains unaltered suggesting that the signal for this match arises in the periphery. With block of arterial flow to the muscle, which decreases venous return without the vascular distension that occurs with venous block, ventilation is no longer linked to oxygen utilization. Thus in this model, the match of ventilation to muscle oxygen use involves distension of the small vessels (or accompanying tissue distortion), which the authors suggest represents a blood flow detector. Natural exercise differs remarkably from the experimental models used to examine the ‘central command’ and ‘peripheral signals’ hypotheses. With central stimulation (‘central command’) breathing does increase along with locomotion but the arterial PCO2 values decrease, and the match is imperfect. While the evidence from ERC experiments is intriguing, it seems unlikely that peripheral signals can be the single cause that links breathing to oxygen consumption in natural exercise given the powerful effects of central stimulation. In natural exercise perhaps ‘central command’ determines an initial match of locomotion and breathing that is modified by feedback from ‘peripheral signals’, an approach alluded to by most workers (Eldridge et al. 1985; Hanna & Kaufman, 2003; Haouzi & Chenuel, 2005). What is new here is the possibility that these ‘peripheral signals’ include a muscle blood flow detector, an intriguing suggestion that will doubtless promote discussion and experimentation.