Document Type


Publication Date


Publication Source

American Journal of Physiology Heart and Circulatory Physiology


We tested the hypothesis that activation of inwardly rectifying potassium (KIR) channels and Na+-K+-ATPase, two pathways that lead to hyperpolarization of vascular cells, contributes to both the onset and steady-state hyperemic response to exercise. We also determined whether after inhibiting these pathways nitric oxide (NO) and prostaglandins (PGs) are involved in the hyperemic response. Forearm blood flow (FBF; Doppler ultrasound) was determined during rhythmic handgrip exercise at 10% maximal voluntary contraction for 5 min in the following conditions: control [saline; trial 1 (T1)]; with combined inhibition of KIR channels and Na+-K+-ATPase alone [via barium chloride (BaCl2) and ouabain, respectively; trial 2(T2)]; and with additional combined nitric oxide synthase (NG-monomethyl-l-arginine) and cyclooxygenase inhibition [ketorolac; trial 3 (T3)]. In T2, the total hyperemic responses were attenuated ∼50% from control (P < 0.05) at exercise onset, and there was minimal further effect in T3 (protocol 1; n= 11). In protocol 2 (n = 8), steady-state FBF was significantly reduced during T2 vs. T1 (133 ± 15 vs. 167 ± 17 ml/min; Δ from control: −20 ± 3%; P < 0.05) and further reduced during T3 (120 ± 15 ml/min; −29 ± 3%; P < 0.05 vs. T2). In protocol 3 (n = 8), BaCl2 alone reduced FBF during onset (∼50%) and steady-state exercise (∼30%) as observed in protocols 1 and 2, respectively, and addition of ouabain had no further impact. Our data implicate activation of KIR channels as a novel contributing pathway to exercise hyperemia in humans.

Inclusive pages




Document Version



The item available for download is the authors' accepted manuscript, deposited as mandated into PubMed Central and provided here in compliance with publisher policies on self-archiving. The version of record is available online.

Permission documentation is on file.

This research was supported by National Heart, Lung, and Blood Institute Grant HL-102720.


American Physiological Society





Link to published version