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 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. 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(IR) and Na+/K+ ATPase in controlling basal tone and in K+-induced vasorelaxation in human forearm resistance vessels.
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 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. 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(IR) and Na+/K+ ATPase in controlling basal tone and in K+-induced vasorelaxation in human forearm resistance vessels.
Authors: Christopher M Hearon; Jennifer C Richards; Mathew L Racine; Gary J Luckasen; Dennis G Larson; Frank A Dinenno Journal: J Physiol Date: 2018-12-26 Impact factor: 5.182
Authors: Christopher M Hearon; Brett S Kirby; Gary J Luckasen; Dennis G Larson; Frank A Dinenno Journal: J Physiol Date: 2016-10-13 Impact factor: 5.182
Authors: Anne R Crecelius; Brett S Kirby; Gary J Luckasen; Dennis G Larson; Frank A Dinenno Journal: Am J Physiol Heart Circ Physiol Date: 2013-05-03 Impact factor: 4.733