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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/H2371    most recent 01279.2007v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dick, G. M. Articles by Tune, J. D. Search for Related Content PubMed PubMed Citation Articles by Dick, G. M. Articles by Tune, J. D.

Voltage-dependent K⁺ channels regulate the duration of reactive hyperemia in the canine coronary circulation

¹Department of Exercise Physiology, Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, West Virginia; ²Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; ³Department of Pediatrics, Baylor College of Medicine, Houston, Texas; and ⁴Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Submitted 1 November 2007 ; accepted in final form 27 March 2008

We previously demonstrated a role for voltage-dependent K⁺ (K_V) channels in coronary vasodilation elicited by myocardial metabolism and exogenous H₂O₂, as responses were attenuated by the K_V channel blocker 4-aminopyridine (4-AP). Here we tested the hypothesis that K_V channels participate in coronary reactive hyperemia and examined the role of K_V channels in responses to nitric oxide (NO) and adenosine, two putative mediators. Reactive hyperemia (30-s occlusion) was measured in open-chest dogs before and during 4-AP treatment [intracoronary (ic), plasma concentration 0.3 mM]. 4-AP reduced baseline flow 34 ± 5% and inhibited hyperemic volume 32 ± 5%. Administration of 8-phenyltheophylline (8-PT; 0.3 mM ic or 5 mg/kg iv) or N^G-nitro-L-arginine methyl ester (L-NAME; 1 mg/min ic) inhibited early and late portions of hyperemic flow, supporting roles for adenosine and NO. 4-AP further inhibited hyperemia in the presence of 8-PT or L-NAME. Adenosine-induced blood flow responses were attenuated by 4-AP (52 ± 6% block at 9 µg/min). Dilation of arterioles to adenosine was attenuated by 0.3 mM 4-AP and 1 µM correolide, a selective K_V1 antagonist (76 ± 7% and 47 ± 2% block, respectively, at 1 µM). Dilation in response to sodium nitroprusside, an NO donor, was attenuated by 4-AP in vivo (41 ± 6% block at 10 µg/min) and by correolide in vitro (29 ± 4% block at 1 µM). K_V current in smooth muscle cells was inhibited by 4-AP (IC₅₀ 1.1 ± 0.1 mM) and virtually eliminated by correolide. Expression of mRNA for K_V1 family members was detected in coronary arteries. Our data indicate that K_V channels play an important role in regulating resting coronary blood flow, determining duration of reactive hyperemia, and mediating adenosine- and NO-induced vasodilation.

ischemic vasodilation; adenosine; 4-aminopyridine; delayed rectifier potassium channel; vascular smooth muscle

This article has been cited by other articles:

				C. L. Heaps, E. C. Jeffery, G. A. Laine, E. M. Price, and D. K. Bowles Effects of exercise training and hypercholesterolemia on adenosine activation of voltage-dependent K+ channels in coronary arterioles J Appl Physiol, December 1, 2008; 105(6): 1761 - 1771. [Abstract] [Full Text] [PDF]