title: Different K+ channels are involved in relaxation of arterial and venous graft induced by nicorandil.
abstract: The drug nicorandil is a vasodilator approved for the treatment of angina. In addition to its well-known effect on the opening of ATP-sensitive K (KATP) channels, nicorandil-induced vasorelaxation also involves the opening of Ca-activated K channels. The aim of this study was to investigate the effects of nicorandil on the isolated human internal mammary artery (HIMA) and the human saphenous vein (HSV) and to define the contribution of different K channel subtypes in the nicorandil action on these arterial and venous grafts. Our results show that nicorandil induced a concentration-dependent relaxation of HSV and HIMA rings precontracted by phenylephrine. Glibenclamide, a selective KATP channels inhibitor, partially inhibited the response to nicorandil in both HSV and HIMA. Iberiotoxin, a most selective blocker of large-conductance Ca-activated K (BKCa) channels, partly antagonized relaxation of HIMA. A nonselective blocker of voltage-gated K channels, 4-aminopyridine caused partial inhibition of the nicorandil-induced relaxation of HSV but did not antagonize relaxation of HIMA induced by nicorandil. Margatoxin, a potent inhibitor of KV1.3 channels, did not abolish the effect of nicorandil on HSV and HIMA. Our results showed that nicorandil induced strong endothelium-independent relaxation of HSV and HIMA contracted by phenylephrine. It seems that KATP and 4-aminopyridine-sensitive K channels located in the smooth muscle of HSV mediated relaxation induced by nicorandil. In addition, KATP and BKCa channels are probably involved in the nicorandil action on HIMA.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. aleksn@pharmacy.bg.ac.rs
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Novakovic
authors.forename: Marija
authors.initials: M
authors.lastname: Pavlovic
authors.forename: Ivan
authors.initials: I
authors.lastname: Stojanovic
authors.forename: Predrag
authors.initials: P
authors.lastname: Milojevic
authors.forename: Milan
authors.initials: M
authors.lastname: Babic
authors.forename: Slavica
authors.initials: S
authors.lastname: Ristic
authors.forename: Nenad
authors.initials: N
authors.lastname: Ugresic
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kanjuh
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: He
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000368:Aged; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D020108:Nicorandil / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D054086:KATP Channels; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D020108:Nicorandil; D015761:4-Aminopyridine