| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Physiology (2001), 537.2, pp. 331
© Copyright 2001 The Physiological Society
 |
Blood pressure rises with exercise. What governs this response? In this issue of The Journal of Physiology, Vissing and colleagues explore the nature of the substances (metabolites?) produced by contracting muscles that stimulate fine afferents in the active muscles and evoke a reflex increase in arterial pressure. Their provocative observations are the latest in over 100 years of investigation on this topic.
In general, two basic, and possibly redundant, mechanisms dominate thinking about blood pressure and exercise. Since blood pressure (and also respiration) increases immediately with the onset of contractions, one idea is that there is a feed-forward 'central command' signal from the brain. This signal is proportional to the motor effort and activates various elements of the autonomic nervous system.
The other main idea is that sympathoexcitatory sensory receptors in the active skeletal muscles are involved in a feed-back reflex. Such receptors might be mechanically sensitive, or they might be 'chemosensitive' and respond to substances from the active muscles. In this way, chemosensitive afferents might sense a mismatch between blood flow and metabolism in the active muscles and evoke an increase in arterial pressure to improve flow. The paper by Vissing et al. (2001) seeks to test the hypothesis that acidosis is the key factor that stimulates the chemosensitive muscle afferents.
In the 1930s, Alam & Smirk (1937, 1938), working in Cairo, showed that the rise in arterial pressure associated with exercise could be augmented if the muscle were ischaemic and much of the increase in pressure (but not heart rate) could be maintained when contractions stopped but the muscle ischaemia continued. This led to the idea that metabolites stimulate muscle afferents and contribute to the rise in arterial pressure with exercise. Studies were then conducted with a patient who had unilateral sensory loss but preserved motor function in one leg. In this patient (Fig. 1) the rise in pressure was robust when the insensitive leg was contracting, but the pressor response was not maintained during post-exercise ischaemia (Alam & Smirk, 1938). This powerful 'experiment in nature' demonstrated that afferents in skeletal muscle can increase arterial pressure. It also provided evidence that central command and feedback from muscle may be redundant control mechanisms.
 |
View larger version [in this window] [in a new window] |
|
|
Figure 1 Figure adapted from Alam & Smirk (1938) showing that a rise in arterial pressure during ischaemic exercise was 'normal' when performed with an 'insensitive' leg, but not maintained by post-exercise muscle ischaemia. | ||
Later, animal experiments by McClosky & Mitchell (1972) confirmed that a metabolically sensitive pressor reflex originated in skeletal muscle. Subsequently, a large number of studies in animals and humans have been conducted in an effort to identify 'the' substance or substances that stimulate the afferents. Studies in anaesthetized animals indicated that while many substances can stimulate the afferents, H+ ions appeared to be the dominant factor (Rotto et al. 1989).
In the 1980s, studies in humans using measurements of muscle sympathetic nerve activity (MSNA) demonstrated that while the onset of exercise was associated with an immediate rise in blood pressure and heart rate, the increase in MSNA took longer to occur and could be sustained (along with the increase in arterial pressure) during post-exercise ischaemia (Mark et al. 1985). The interpretation was that the rise in MSNA was linked to the activation of the chemosensitive afferents. Later, Victor and colleagues (1988) showed that MSNA began to rise in human volunteers during exercise when the pH in the active muscles started to fall. In patients with McArdle's disease, who lack the enzyme required to break down glycogen and do not produce lactic acid, there was no increase in MSNA during fatiguing muscle contractions (Pryor et al. 1990). This observation seemed to 'establish' muscle acidosis as the main factor that stimulates blood pressure-raising sensory afferents in contracting skeletal muscle.
However, in the study by Vissing et al. (2001), similar patients with McArdle's disease were studied, and these patients showed a rise in MSNA with contractions. These subjects performed arm flexion exercise (as opposed to handgripping) and demonstrated a robust increase in MSNA with exercise that was sustained during post-exercise ischaemia. This rise occurred even though the muscles did not acidify. Since the studies by both Pryor et al. (1990) and Vissing et al. (2001) appear to have been carefully done, how can these observations be reconciled? Unless unappreciated differences in experimental design are responsible, the simple answer is that they cannot be reconciled. While the evidence that acidosis is a key physiological stimulator of chemosensitive afferents in muscle seems quite strong (Victor et al. 1988; Rotto et al. 1989; Pryor et al. 1990), the data presented by Vissing et al. (2001) at a minimum suggest that H+ ions are not obligatory.
Thus, a 'closed' question is 're-opened' and old questions about what substances from exercising muscle stimulate the fine chemosensitive muscle afferents are new again. Finally, in an era of transgenic animals and molecular medicine, the observations in this paper demonstrate the power of integrative physiology studies in unusual human patients.
|
REFERENCES |
|---|
| ALAM, M. & SMIRK, F. H. (1937). Journal of Physiology 89, 372-383 | |
| ALAM, M. & SMIRK, F. H. (1938). Clinical Science 3, 247-252 | |
| MCCLOSKEY, D. I. & MITCHELL, J. H. (1972). Journal of Physiology 224, 173-186 | [Medline] |
| MARK, A. L., VICTOR, R. G., NERHED, C. & WALLIN, B. G. (1985). Circulation Research 57, 461-469 | [Abstract] |
| PRYOR, S. L., LEWIS, S. F., HALLER, R. G., BERTOCCI, L. A. & VICTOR, R. G. (1990). Journal of Clinical Investigation 85, 1444-1449 | [Medline] |
| ROTTO, D. M., STEBBINS, C. L. & KAUFMAN, M. P. (1989). Journal of Applied Physiology 67, 256-263 | [Medline] |
| VICTOR, R. G., BERTOCCI, L. A., PRYOR, S. L. & NUNNALLY, R. L. (1988). Journal of Clinical Investigation 82, 1301-1305 | [Medline] |
| VISSING, J., MACLEAN, D. A., VISSING, S. F., SANDER, M., SALTIN, B. & HALLER, R. G. (2001). Journal of Physiology 537, 641-649 | [Abstract/Full Text] |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
