Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado;
Medical Center of the Rockies Foundation, University of Colorado Health, Loveland, Colorado.
Am J Physiol Heart Circ Physiol. 2014 Sep 1;307(5):H782-91. doi: 10.1152/ajpheart.00212.2014. Epub 2014 Jun 27.
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.
我们测试了这样一个假设，即内向整流钾 (KIR) 通道和 Na(+)-K(+)-ATP 酶的激活——这两条途径可导致血管细胞超极化——有助于运动引起的起始和稳态充血反应。我们还确定了在抑制这些途径后，一氧化氮 (NO) 和前列腺素 (PGs) 是否参与了充血反应。在前臂血流 (FBF；超声多普勒) 在以下条件下，通过 10%最大自主收缩的节律性手握运动 5 分钟进行测定：对照 [盐水；试验 1 (T1)]；同时单独抑制 KIR 通道和 Na(+)-K(+)-ATP 酶[分别用氯化钡 (BaCl2) 和哇巴因；试验 2 (T2)]；以及额外的一氧化氮合酶 (N(G)-单甲基-L-精氨酸) 和环氧化酶抑制[酮咯酸；试验 3 (T3)]。在 T2 中，与对照相比，运动起始时总充血反应降低了约 50%（P < 0.05），而在 T3 中则没有进一步的影响（方案 1；n = 11）。在方案 2（n = 8）中，与 T1 相比，T2 期间稳态 FBF 显著降低（133 ± 15 与 167 ± 17 ml/min；与对照相比的 Δ：-20 ± 3%；P < 0.05），而在 T3 期间进一步降低（120 ± 15 ml/min；-29 ± 3%；P < 0.05 与 T2）。在方案 3（n = 8）中，如方案 1 和 2 中观察到的，BaCl2 单独降低了运动起始时的 FBF（约 50%）和稳态运动时的 FBF（约 30%），而哇巴因的添加没有进一步的影响。我们的数据表明，KIR 通道的激活是人类运动性充血的一种新的贡献途径。
