Progressive handgrip exercise: evidence of nitric oxide-dependent vasodilation and blood flow regulation in humans.

In the peripheral circulation, nitric oxide (NO) is released in response to shear stress across vascular endothelial cells. We sought to assess the degree to which NO contributes to exercise-induced vasodilation in the brachial artery (BA) and to determine the potential of this approach to noninvasively evaluate NO bioavailability. In eight young (25 ± 1 yr) healthy volunteers, we used ultrasound Doppler to examine BA vasodilation in response to handgrip exercise (4, 8, 12, 16, 20, and 24 kg) with and without endothelial NO synthase blockade [intra-arterial N(G)-monomethyl-L-arginine (L-NMMA), 0.48 mg · dl(-1) · min(-1)]. Higher exercise intensities evoked significant BA vasodilation (4-12%) that was positively correlated with the hyperemic stimulus (r = 0.98 ± 0.003, slope = 0.005 ± 0.001). During NO blockade, BA vasodilation at the highest exercise intensity was reduced by ∼70% despite similar exercise-induced increases in shear rate (control, +224 ± 30 s(-1); L-NMMA, +259 ± 46 s(-1)). The relationship and slope of BA vasodilation with increasing shear rate was likewise reduced (r = 0.48 ± 0.1, slope = 0.0007 ± 0.0005). We conclude that endothelial NO synthase inhibition with L-NMMA abolishes the relationship between shear stress and BA vasodilation during handgrip exercise, providing clear evidence of NO-dependent vasodilation in this experimental model. These results support this paradigm as a novel and valid approach for a noninvasive assessment of NO-dependent vasodilation in humans.