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POINT-COUNTERPOINT COMMENTS

Comment on Point:Counterpoint "Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function"

Department of Anesthesiology
Mayo Clinic
Rochester, Minnesota

This letter is in response to the Point-Counterpoint series "Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function." that appeared in the September issue (vol. 99: 1233–1238, 2005; doi:10.1152/japplphysiol.00601; http://jap.physiology.org/content/vol99/issue3).

To the Editor: The exchange by Drs. Green and Tschakovsky (2) highlight some specific issues and limitations related to the use, misuse, and over-extrapolation of brachial artery flow-mediated dilation (FMD) as a tool to noninvasively assess "endothelial function" in humans. FMD can be influenced by sympathetic tone and the magnitude of the shear stress evoked by the reactive hyperemia (3, 4). Additionally, these modifiers of FMD can differ in a number of conditions and diseases where FMD, and hence "endothelial" function, also differ. More importantly, there is also no relationship between more direct pharmacological tests of endothelial function in the forearm and FMD (1). All of these concerns raise questions about how robustly FMD reflects endothelial function.

With these limitations in mind, why are measures of FMD so "popular"? First, the technique is noninvasive. Second, it can be performed by technicians using equipment available in clinical labs. Third, it can be done on a high-throughput basis. Fourth, and perhaps most importantly, sophisticated integrative physiology techniques frequently seem to be a lost art in clinical investigation. That having been said, is it better to perform detailed, invasive, and time consuming physiological investigations that provide clear mechanistic insight on a limited number of subjects? Or do we continue to let screening tests on large numbers of subjects serve as over-simplified surrogate markers for complex biological events? Understanding how new mechanisms discovered in reductionist preparations contribute to physiological and pathophysiological events will require clinical investigators to relearn how to do integrative physiology in humans.

FOOTNOTES

e-mail: joyner.michael{at}mayo.edu

REFERENCES

1. Eskurza I, Seals DR, DeSouza CA, and Tanaka H. Pharmacologic versus flow-mediated assessments of peripheral vascular endothelial vasodilatory function in humans. Am J Cardiol 88: 1067–1069, 2001.[CrossRef][Web of Science][Medline]
2. Green D; Tschakovsky ME and Pyke KE. Point:Counterpoint. Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function. J Appl Physiol 99: 1233–1238, 2005.[Free Full Text]
3. Hijmering ML, Stroes ESGIO, Iijhoek J, Hutten BA, Blankestijn PJ, and Rebelink TJ. Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation. J Am Coll Cardiol 39: 683–688, 2002.[Abstract/Free Full Text]
4. Pyke KE, Dwyer EM, and Tschakovsky ME. Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans. J Appl Physiol 97: 499–508, 2004.[Abstract/Free Full Text]

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