Published Online
on February 25, 2002

A more recent version of this article appeared on March 19, 2002

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Submitted on January 9, 2002
Accepted on January 11, 2002

Barium Reduces Resting Blood Flow and Inhibits Potassium-Induced Vasodilation in the Human Forearm

Matthew Dawes PhD, MRCP, Christine Sieniawska BSc, MPhil, Trevor Delves PhD, CChem, EurClinChem, FRSC, Rahul Dwivedi MRCP, Philip J. Chowienczyk FRCP, and James M. Ritter MA, DPhil, FRCP^*

From the Department of Clinical Pharmacology and Centre for Cardiovascular Biology and Medicine, King's College, London, UK (M.D., R.D., P.J.C., J.M.R.), and SAS Trace Element Unit, Chemical Pathology, Southampton University Hospitals NHS Trust, Southampton, UK (C.S., T.D.).

^* To whom correspondence should be addressed. E-mail: james.ritter{at}kcl.ac.uk.

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 µmol/min, also used in subsequent experiments) increased Ba²⁺ plasma concentration in the infused forearm to 50±0.8 µmol/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 P0.01). 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.

Key words: potassium • vasodilation • endothelium-derived factors • muscle, smooth • vasculature

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