Muscle Cramps and Nitric Oxide
Muscle Cramps and Nitric Oxide
Abstract & Commentary
Synopsis: A link is shown between increased levels of nitric oxide, strenuous exercise, and severe muscle cramps.
Source: Maddali S, et al. Postexercise increase in nitric oxide in football players with muscle cramps. Am J Sports Med 1998; 26(6):820-824.
Nitric oxide, a free radical functioning as an intracellular and intercellular messenger molecule, has been shown to have important roles in vasodilatation, platelet aggregation, cardiac contractility, and host defense against infection.1 The enzyme, nitric oxide synthase, is abundant in skeletal muscle, and nitric oxide appears to have important functions for this tissue as well.
Maddali and colleagues analyzed detailed blood chemistries for members of the New York Giants football team before and during rigorous preseason "two-a-day" practices. They found that nitrite, the stable breakdown product of nitric oxide, increased nearly 300% in those players suffering severe, generalized muscle cramps and symptoms of heat exhaustion requiring intravenous rehydration. Other serum chemistries showed much smaller variations consistent with dehydration.
Maddali et al also determined that players with a greater mean weight and percentage of body fat tended to lose more weight during each practice and were at greater risk of cramps requiring rehydration.
Because the dramatic, threefold increase in nitrite did not correlate statistically with the other serum chemistries, and because other values increased to a much smaller degree (16% for albumin, 102% for lactate dehydrogenase), the nitrite increase appeared specific to muscle cramps rather than just dehydration. Compared with only a 51% increase in creatinine from the expected rhabdomyolysis, the 300% increase in nitrite reflects increased nitric oxide synthesis.
Comment by David R. Diduch, MS, MD
Maddali et al have clearly demonstrated a link between increased levels of nitric oxide, strenuous exercise, and severe muscle cramps. The precise relationship between nitric oxide and cramps remains unclear and requires further research. Without further data from players without cramps, it is also unclear whether the cramps, the exercise, or both generated the increase in nitric oxide.
This study, combined with others in the literature, can lead to a plausible explanation for the role of nitric oxide in muscle cramping. Extreme exercise induces vasodilatation to increase blood flow to muscles and dissipate body heat.2 Nitric oxide is released from endothelial cells and skeletal muscle cells.3 This increased nitric oxide enhances further vasodilatation, skeletal muscle contractility, and increases in body temperature. Hyperemia adds to the problem of dehydration. The contribution of nitric oxide and its metabolites to skeletal muscle cramps may be related to increased contractility but needs further exploration.4
There has been a recent surge in the use of nutritional supplements such as creatine that are known to promote dehydration. Creatine increases intracellular skeletal muscle water in response to increased protein levels within the cells. Severe, generalized muscle cramps are becoming extremely common with less strenuous exercise because of the increased propensity to dehydration. The sports medicine physician must be aware of this relationship between creatine and dehydration and be alert to the need for prompt rehydration should symptoms occur. Further research is needed to better understand these relationships, optimize treatment, and minimize potential consequences.
References
1. Murrell GAC, et al. Nitric oxide: An important articular free radical. J Bone Joint Surg 1996;78A: 265-274.
2. Matsumoto A, et al. Increased nitric oxide production during exercise. Lancet 1994;343:849-850.
3. Murrant CL, Barclay JK. Endothelial cell products alter mammalian skeletal muscle function in vitro. Can J Physiol Pharmacol 1995;73:736-741.
4. Kobzik L, et al. Nitric oxide in skeletal muscles. Nature 1994;372:546-548.
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