Barium reduces resting blood flow and inhibits potassium-induced vasodilation in the human forearm

Background-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. Methods and Results-Blood flow was measured by plethysmography in healthy men. Drugs and electrolytes were infused through the brachial artery. BaCl2 (4 mumol/min, also used in subsequent experiments) increased Ba2+ plasma concentration in the infused forearm to 50 +/- 0.8 mumol/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 Pless than or equal to0.01). 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. Conclusions-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, and Na+/K+ ATPase in controlling basal tone and in K+-induced vasorelaxation in human forearm resistance vessels.