This Article Full Text Full Text (PDF) All Versions of this Article: 105/11/1323    most recent hc1102.105651v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dawes, M. Articles by Ritter, J. M. Search for Related Content PubMed PubMed Citation Articles by Dawes, M. Articles by Ritter, J. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB BARIUM COMPOUNDS BARIUM, ELEMENTAL OUABAIN POTASSIUM VERAPAMIL HYDROCHLORIDE Related Collections Hypertension - basic studies Clinical Studies Platelets Endothelium/vascular type/nitric oxide

(Circulation. 2002;105:1323.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

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; 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.).

Correspondence to Prof J.M. Ritter, Department of Clinical Pharmacology, Block 5, South Wing, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK. 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

This article has been cited by other articles:

				A. A. Quyyumi and M. Ozkor Vasodilation by Hyperpolarization: Beyond NO Hypertension, December 1, 2006; 48(6): 1023 - 1025. [Full Text] [PDF]

				J. Li, L. I. Sinoway, and Y.-C. Ng Aging augments interstitial K+ concentrations in active muscle of rats J Appl Physiol, April 1, 2006; 100(4): 1158 - 1163. [Abstract] [Full Text] [PDF]

				F. J. Haddy, P. M. Vanhoutte, and M. Feletou Role of potassium in regulating blood flow and blood pressure Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R546 - R552. [Abstract] [Full Text] [PDF]

				R. Dwivedi, S. Saha, P.J. Chowienczyk, and J.M. Ritter Block of Inward Rectifying K+ Channels (KIR) Inhibits Bradykinin-Induced Vasodilatation in Human Forearm Resistance Vasculature Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): e7 - e9. [Abstract] [Full Text] [PDF]

				Z. Zhu, S. Zhu, D. Liu, T. Cao, L. Wang, and M. Tepel Thiazide-Like Diuretics Attenuate Agonist-Induced Vasoconstriction by Calcium Desensitization Linked to Rho Kinase Hypertension, February 1, 2005; 45(2): 233 - 239. [Abstract] [Full Text] [PDF]

				K. Goto, N. M Rummery, T. H. Grayson, and C. E Hill Attenuation of conducted vasodilatation in rat mesenteric arteries during hypertension: role of inwardly rectifying potassium channels J. Physiol., November 15, 2004; 561(1): 215 - 231. [Abstract] [Full Text] [PDF]

				R. Schubert, U. Krien, I. Wulfsen, D. Schiemann, G. Lehmann, N. Ulfig, R. W. Veh, J. R. Schwarz, and H. Gago Nitric Oxide Donor Sodium Nitroprusside Dilates Rat Small Arteries by Activation of Inward Rectifier Potassium Channels Hypertension, April 1, 2004; 43(4): 891 - 896. [Abstract] [Full Text] [PDF]

				J. E. Macdonald and A. D. Struthers What is the optimal serum potassium level in cardiovascular patients? J. Am. Coll. Cardiol., January 21, 2004; 43(2): 155 - 161. [Abstract] [Full Text] [PDF]

				S. Vigili de Kreutzenberg, E. Kiwanuka, A. Tiengo, and A. Avogaro Visceral obesity is characterized by impaired nitric oxide-independent vasodilation Eur. Heart J., July 1, 2003; 24(13): 1210 - 1215. [Abstract] [Full Text] [PDF]