Differential antivasoconstrictor effects of levcromakalim and rilmakalim on the isolated human mammary artery and saphenous vein.
It is well established that spasm of an arterial and venous graft conduit may occur during harvesting or after coronary artery bypass grafting (CABG). The antivasoconstrictor effect of levcromakalim and rilmakalim, K(+) channel openers (KCOs), was studied in isolated human internal mammary artery (HIMA) and human saphenous vein (HSV) prepared for CABG. HIMA and HSV rings were contracted by electrical field stimulation (EFS, 20 Hz ) or with exogenous noradrenaline (NA). Levcromakalim induced a concentration-dependent and equipotent inhibition of contraction of HIMA and HSV preconstricted by EFS and exogenoulsy applied NA, while rilmakalim produced a stronger inhibition of EFS- than NA-evoked contractions. Glibenclamide, a selective ATP-sensitive K(+) channel (K(ATP) channel) blocker, significantly antagonized levcromakalim-induced inhibition of EFS- and NA-evoked contractions, as well as rilmakalim-induced inhibiton of EFS-evoked contractions on HIMA and HSV. However, glibenclamide failed to antagonize rilmakalim-induced inhibition of NA-evoked contractions. The results suggest that the antivasoconstrictor effect of levcromakalim occurs postsynapticaly by the opening K(ATP) channels in the vascular smooth muscle cells. They also suggest that the effect of rilmakalim on EFS-evoked contractions involves K(ATP) channels located pre-synaptically. However, the mechanism by which rilmakalim inhibits NA-evoked contraction seems to be K(ATP) channel independent and warrants further elucidation.
Novaković
Aleksandra
A
Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia and Montenegro.
Gojković-Bukarica
Ljiljana
L
Beleslin-Cokić
Bojana
B
Japundzić-Zigon
Nina
N
Sajić
Zoran
Z
Nezić
Dusan
D
Perić
Miodrag
M
Djukanović
Bosko
B
Kazić
Tomislav
T
D002839:Chromans / Q000494:pharmacology*; D019806:Cromakalim / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D002839:Chromans; D011759:Pyrrolidines; D014662:Vasoconstrictor Agents; D019806:Cromakalim; C075012:rilmakalim