Dawes Matthew, Sieniawska Christine, Delves Trevor, Dwivedi Rahul, Chowienczyk Philip J, Ritter James M
Department of Clinical Pharmacology and Centre for Cardiovascular Biology and Medicine, King's College, London, UK.
Circulation. 2002 Mar 19;105(11):1323-8. doi: 10.1161/hc1102.105651.
Increasing extracellular K+ concentration within and just above the physiological range hyperpolarizes and relaxes vascular smooth muscle in vitro. These actions involve inwardly rectifying potassium channels (K(IR)) and Na+/K+ ATPase, which are inhibited, respectively, by Ba2+ and ouabain. The role (if any) of K(IR) in controlling human resistance vessel tone is unknown, and we investigated this in the forearm.
Blood flow was measured by plethysmography in healthy men. Drugs and electrolytes were infused through the brachial artery. BaCl2 (4 micromol/min, also used in subsequent experiments) increased Ba2+ plasma concentration in the infused forearm to 50+/-0.8 micromol/L (mean+/-SEM) and reduced blood flow by 24+/-4% (n=8, P<0.001) without causing systemic effects. Ouabain (2.7 nmol/min), alone and with BaCl2, reduced flow by 10+/-2% and 28+/-3%, respectively (n=10). Incremental infusions of KCl (0.05, 0.1, and 0.2 mmol/min) increased flow from baseline by 1.0+/-0.2, 2.0+/-0.4, and 4.2+/-0.5 mL/min per deciliter forearm, respectively. Responses to KCl (0.2 mmol/min) were inhibited by BaCl2, alone and plus ouabain, by 60+/-9% and 88+/-6%, respectively (both P< or =0.01). In control experiments, norepinephrine (240 pmol/min) reduced blood flow by 24+/-2% but had no significant effect on K+-induced vasodilation. BaCl2, alone or with ouabain, did not significantly influence responses to verapamil or nitroprusside.
Ba2+ increases forearm vascular resistance. K+-induced vasodilation is selectively inhibited by Ba2+ and almost abolished by Ba2+ plus ouabain, suggesting a role for K(IR) and Na+/K+ ATPase in controlling basal tone and in K+-induced vasorelaxation in human forearm resistance vessels.
在体外，将细胞外钾离子浓度增加至略高于生理范围会使血管平滑肌发生超极化并舒张。这些作用涉及内向整流钾通道（K(IR)）和钠钾ATP酶，它们分别被钡离子和哇巴因抑制。K(IR)在控制人体阻力血管张力方面的作用（如果有）尚不清楚，我们在前臂对此进行了研究。
通过体积描记法测量健康男性的血流量。药物和电解质通过肱动脉输注。氯化钡（4微摩尔/分钟，后续实验也使用此剂量）使输注前臂的血浆钡离子浓度升高至50±0.8微摩尔/升（平均值±标准误），并使血流量减少24±4%（n = 8，P<0.001），且未产生全身效应。哇巴因（2.7纳摩尔/分钟）单独使用以及与氯化钡联合使用时，分别使血流量减少10±2%和28±3%（n = 10）。递增输注氯化钾（0.05、0.1和0.2毫摩尔/分钟）使前臂每分升血流量较基线分别增加1.0±0.2、2.0±0.4和4.2±0.5毫升/分钟。单独使用氯化钡以及联合使用哇巴因时，对氯化钾（0.2毫摩尔/分钟）的反应分别被抑制60±9%和88±6%（均P≤0.01）。在对照实验中，去甲肾上腺素（240皮摩尔/分钟）使血流量减少24±2%，但对钾离子诱导的血管舒张无显著影响。氯化钡单独使用或与哇巴因联合使用，对维拉帕米或硝普钠的反应均无显著影响。
钡离子增加前臂血管阻力。钾离子诱导的血管舒张被钡离子选择性抑制，被钡离子加哇巴因几乎完全消除，提示K(IR)和钠钾ATP酶在控制人体前臂阻力血管的基础张力以及钾离子诱导的血管舒张中起作用。
