Mechanisms of Rapid Vasodilatation Following a Brief Contraction in Human Skeletal Muscle

Anne R. Crecelius, University of Dayton
Brett S. Kirby, Duke University Medical Center
Gary J. Luckasen, Medical Center of the Rockies Foundation
Dennis G. Larson, Medical Center of the Rockies Foundation
Frank A. Dinenno, Colorado State University - Fort Collins

Publisher citation
Anne R. Crecelius, Brett S. Kirby, Gary J. Luckasen, Dennis G. Larson, Frank A. Dinenno. "Mechanisms of Rapid Vasodilatation Following a Brief Contraction in Human Skeletal Muscle." American Journal of Physiology - Heart and Circulatory Physiology. Jul 2013, 305(1) H29-H40

Article also available at PubMed Central


A monophasic increase in skeletal muscle blood flow is observed after a brief single forearm contraction in humans, yet the underlying vascular signaling pathways remain largely undetermined. Evidence from experimental animals indicates an obligatory role of vasodilation via K+-mediated smooth muscle hyperpolarization, and human data suggest little to no independent role for nitric oxide (NO) or vasodilating prostaglandins (PGs). We tested the hypothesis that K+-mediated vascular hyperpolarization underlies the rapid vasodilation in humans and that combined inhibition of NO and PGs would have a minimal effect on this response. We measured forearm blood flow (Doppler ultrasound) and calculated vascular conductance 10 s before and for 30 s after a single 1-s dynamic forearm contraction at 10%, 20%, and 40% maximum voluntary contraction in 16 young adults. To inhibit K+-mediated vasodilation, BaCl2 and ouabain were infused intra-arterially to inhibit inwardly rectifying K+ channels and Na+-K+-ATPase, respectively. Combined enzymatic inhibition of NO and PG synthesis occurred via NG-monomethyl-l-arginine (l-NMMA; NO synthase) and ketorolac (cyclooxygenase), respectively. In protocol 1 (n = 8), BaCl2 + ouabain reduced peak vasodilation (range: 30–45%, P < 0.05) and total postcontraction vasodilation (area under the curve, ∼55–75% from control) at all intensities. Contrary to our hypothesis, l-NMMA + ketorolac had a further impact (peak: ∼60% and area under the curve: ∼80% from control). In protocol 2 (n = 8), the order of inhibitors was reversed, and the findings were remarkably similar. We conclude that K+-mediated hyperpolarization and NO and PGs, in combination, significantly contribute to contraction-induced rapid vasodilation and that inhibition of these signaling pathways nearly abolishes this phenomenon in humans.