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

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American Journal of Physiology - Heart and Circulatory Physiology


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.

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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

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hyperemia, exercise, potassium