title: Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts.
abstract: As we previously demonstrated the role of different K(+) channels in the action of nicorandil on human saphenous vein (HSV) and human internal mammary artery (HIMA), this study aimed to analyse the contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K(+) channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K(+) (KATP) channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K(+) (KV) channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca(2+)-activated K(+) (BKCa) channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of KV channels in HSV is probably due to GC activation and increased levels of cGMP.
authors: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors: Marija
authors: M
authors: Marinko
authors: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. Electronic address: aleksn@pharmacy.bg.ac.rs.
authors: Aleksandra
authors: A
authors: Novakovic
authors: Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia.
authors: Dragoslav
authors: D
authors: Nenezic
authors: Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia.
authors: Ivan
authors: I
authors: Stojanovic
authors: Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia.
authors: Predrag
authors: P
authors: Milojevic
authors: Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia.
authors: Miomir
authors: M
authors: Jovic
authors: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors: Nenad
authors: N
authors: Ugresic
authors: Academy of Sciences and Arts, Belgrade, Serbia.
authors: Vladimir
authors: V
authors: Kanjuh
authors: Department of Surgery, The Chinese University of Hong Kong, Hong Kong; TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China.
authors: Qin
authors: Q
authors: Yang
authors: TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China; Providence Heart & Vascular Institute, Albert Starr Academic Center, Department of Surgery, Oregon Health and Science University, Portland, OR, USA.
authors: Guo-Wei
authors: GW
authors: He
mesh_terms: D000368:Aged; D001026:Coronary Artery Bypass; D006152:Cyclic GMP / Q000502:physiology*; D006162:Guanylate Cyclase / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects*; D008875:Middle Aged; D020108:Nicorandil / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D012501:Saphenous Vein / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D054086:KATP Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D014665:Vasodilator Agents; D020108:Nicorandil; D006162:Guanylate Cyclase; D006152:Cyclic GMP
keywords: Cyclic GMP; Human bypass grafts; K channel; Nicorandil; Vasorelaxation