Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation?

We investigated the independent contributions of the peak and continued reactive hyperemia on flow-mediated dilation (FMD). 1) For the duration manipulation experiment (DME), 10 healthy males experienced reactive hyperemia durations of 10 s, 20 s, 30 s, 40 s, 50 s, or full reactive hyperemia (RH). 2) For the peak manipulation experiment (PME), eight healthy males experienced reactive hyperemia trials with three peak shear rate magnitudes (large, medium, and small). Data are means +/- SD. For the DME, peak shear rate was not different between trials (P = 0.326). Shear rate area under the curve (AUC) was P < 0.001. Peak %FMD was dependent on shear rate AUC: 10 s, 2.7 +/- 1.3; 20 s, 6.2 +/- 1.9; 30 s, 7.9 +/- 2.9; 40 s, 8.3 +/- 3.2; 50 s, 7.9 +/- 3.2; full RH, 9.3 +/- 4.1, with 10 and 20 s less than full RH (P < 0.001). For the PME, peak shear rate was different between trials (large, 1,049.1 +/- 285.8; medium, 726.4 +/- 228.8; small, 512.8 +/- 161.8; P < 0.001). AUC of the continued shear rate was not (P = 0.412). Peak %FMD was unaffected by peak shear rate (large, 7.0 +/- 2.7%; medium, 7.4 +/- 2.6%; small, 6.6 +/- 1.8%; P = 0.542). Peak and AUC shear stimulus were not significantly related in full RH (r(2) = 0.35, P = 0.07). We conclude that the shear stimulus AUC, not the peak itself, is the critical determinant of the peak FMD response. This indicates AUC as the best method of quantifying reactive hyperemia shear stimulus for %FMD normalization.