title: Voltage-dependent K+ channels regulate the duration of reactive hyperemia in the canine coronary circulation.
abstract: We previously demonstrated a role for voltage-dependent K(+) (K(V)) channels in coronary vasodilation elicited by myocardial metabolism and exogenous H(2)O(2), 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 microg/min). Dilation of arterioles to adenosine was attenuated by 0.3 mM 4-AP and 1 microM correolide, a selective K(V)1 antagonist (76 +/- 7% and 47 +/- 2% block, respectively, at 1 microM). Dilation in response to sodium nitroprusside, an NO donor, was attenuated by 4-AP in vivo (41 +/- 6% block at 10 microg/min) and by correolide in vitro (29 +/- 4% block at 1 microM). K(V) current in smooth muscle cells was inhibited by 4-AP (IC(50) 1.1 +/- 0.1 mM) and virtually eliminated by correolide. Expression of mRNA for K(V)1 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.
authors: Department of Exercise Physiology, Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, WV, USA.
authors: Gregory M
authors: GM
authors: Dick
authors: Ian N
authors: IN
authors: Bratz
authors: Léna
authors: L
authors: Borbouse
authors: Gregory A
authors: GA
authors: Payne
authors: U Deniz
authors: UD
authors: Dincer
authors: Jarrod D
authors: JD
authors: Knudson
authors: Paul A
authors: PA
authors: Rogers
authors: Johnathan D
authors: JD
authors: Tune
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006940:Hyperemia / Q000378:metabolism* / Q000503:physiopathology; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger / Q000032:analysis; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D054086:KATP Channels; D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D014315:Triterpenes; C118657:correolide; D009599:Nitroprusside; D009569:Nitric Oxide; D015761:4-Aminopyridine; D013806:Theophylline; C028322:8-phenyltheophylline; D019001:Nitric Oxide Synthase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester