title: KIR channel activation contributes to onset and steady-state exercise hyperemia in humans.
abstract: 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 (N(G)-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.
authors: Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado;
authors: Anne R
authors: AR
authors: Crecelius
authors: Medical Center of the Rockies Foundation, University of Colorado Health, Loveland, Colorado.
authors: Gary J
authors: GJ
authors: Luckasen
authors: Medical Center of the Rockies Foundation, University of Colorado Health, Loveland, Colorado.
authors: Dennis G
authors: DG
authors: Larson
authors: Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado; Vascular Physiology Research Group, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado; and Frank.Dinenno@ColoState.edu.
authors: Frank A
authors: FA
authors: Dinenno
mesh_terms: D000328:Adult; D017609:Barium Compounds / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015444:Exercise; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006940:Hyperemia / Q000378:metabolism*; D020910:Ketorolac / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D010042:Ouabain / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D012039:Regional Blood Flow; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011453:Prostaglandins; C024986:barium chloride; D009569:Nitric Oxide; D010042:Ouabain; D052250:Nitric Oxide Synthase Type III; D000254:Sodium-Potassium-Exchanging ATPase; D019331:NG-Nitroarginine Methyl Ester; D020910:Ketorolac
keywords: blood flow; contraction; skeletal muscle; vasodilation