title: The effects of potassium channel opener P1075 on the human saphenous vein and human internal mammary artery.
abstract: Because adrenergic contractions can contribute to the development of life-threatening spasm of coronary artery bypass graft, this study was performed to investigate the effect of adenosine 3-phosphate (ATP)-sensitive K channel (KATP) opener P1075 on contractions of isolated human saphenous vein (HSV) and human internal mammary artery (HIMA). Phasic contractions were evoked by electric field stimulation (20 Hz) and noradrenaline. The sustained contractions were evoked by phenylephrine. The presence of pore-forming Kir6.1 and Kir6.2 subunits of the KATP channels in the HIMA and only Kir6.2 in the HSV was confirmed immunomorphologically. P1075 inhibited in the HSV only, the electrical field stimulation contractions more strongly than noradrenaline contractions. In addition, the phenylephrine contractions of HSV were more sensitive to P1075 in comparison to those of HIMA. Glibenclamide, a KATP channel blocker antagonized the vasodilatation produced by P1075 in both grafts differently, because its effect was more prominent on the P1075-induced inhibition of contractions of HSV than of HIMA. We conclude that P1075 has a vasorelaxant effect and inhibited adrenergic contractions of the tested grafts. This effect is graft and vasoconstrictor selective and seems to be mediated by Kir6.1- and/or Kir6.2-containing KATP channels. Thus, P1075 can be considered as a potential drug in the prevention of graft spasm.
authors.affiliation: Department of Clinical Pharmacology, Pharmacology and Toxicology, Faculty of Medicine, University Belgrade, Belgrade, Serbia. l.g.bukarica@sezampro.rs
authors.forename: Ljiljana C
authors.initials: LC
authors.lastname: Gojkovic-Bukarica
authors.forename: Bojana B
authors.initials: BB
authors.lastname: Beleslin-Cokic
authors.forename: Aleksandra N
authors.initials: AN
authors.lastname: Novakovic
authors.forename: Miodrag S
authors.initials: MS
authors.lastname: Peric
authors.forename: Jasmina Z
authors.initials: JZ
authors.lastname: Markovic-Lipkovski
authors.forename: Sanja Z
authors.initials: SZ
authors.lastname: Cirovic
authors.forename: Dusan G
authors.initials: DG
authors.lastname: Nezic
authors.forename: Aleksandar R
authors.initials: AR
authors.lastname: Lesic
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Kanjuh
authors.forename: Helmut
authors.initials: H
authors.lastname: Heinle
mesh_terms: D000368:Aged; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D054086:KATP Channels / Q000819:agonists* / Q000378:metabolism; D008297:Male; D008323:Mammary Arteries / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D009924:Organ Culture Techniques; D009928:Organ Specificity; D009994:Osmolar Concentration; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012501:Saphenous Vein / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000099161:Kcnj11 Channel
chemical_list: D005905:Glyburide; D006146:Guanidines; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; D011725:Pyridines; D014665:Vasodilator Agents; D000099161:Kcnj11 Channel; C092520:uK-ATP-1 potassium channel; C073896:N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine