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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:e7.)
© 2005 American Heart Association, Inc.

Vascular Biology

Block of Inward Rectifying K⁺ Channels (K_IR) Inhibits Bradykinin-Induced Vasodilatation in Human Forearm Resistance Vasculature

R. Dwivedi; S. Saha; P.J. Chowienczyk; J.M. Ritter

From the Department of Clinical Pharmacology, GKT Division of Cardiovascular Medicine, St Thomas’ Hospital, London, United Kingdom.

Correspondence to J.M. Ritter, Department of Clinical Pharmacology, St Thomas’ Hospital, Lambeth Palace Road, London, SE1 7EH, UK. E-mail james.ritter{at}kcl.ac.uk

Objective— To investigate the possible involvement of inward rectifying K⁺ channels (K_IR) in the response of human resistance vessels to bradykinin in vivo.

Methods and Results— Drugs were administered via the brachial artery in healthy male volunteers and forearm blood flow was measured by venous occlusion plethysmography. Inhibition of K_IR by barium chloride (4 µmol min^–1) alone or with additional inhibition of Na⁺/K⁺ ATPase (ouabain 2.7 µmol min^–1) reduced responses to bradykinin (30 pmol min^–1), by 26±8.3% and 36±7.2%, respectively (each P<0 0.05). Barium with ouabain plus inhibitors of prostaglandin (PG) and nitric oxide synthesis inhibited but did not abolish responses to bradykinin (51±2.8% inhibition; P<0.01); norepinephrine (240 pmol min^–1) caused similar reduction of baseline blood flow, as did this combination of inhibitors, but did not significantly inhibit the response to bradykinin. Barium plus ouabain did not significantly reduce responses to acetylcholine or albuterol.

Conclusion— A component of the vasodilator response to bradykinin in human forearm vasculature is mediated by K_IR.

The possible involvement of inward-rectifying K⁺ channels (K_IR) in the action of bradykinin was investigated by administering drugs via the brachial artery in healthy men. Barium selectively inhibited the forearm blood flow response to bradykinin, indicating that a component of this response is mediated by K_IR.

Key Words: bradykinin • barium • forearm vasculature • inward-rectifying potassium channels • hyperpolarizing factor

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