Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo

Background: levosimendan and its long-lived metabolite or-1896 produce vasodilation in different types of vessels by activating atp-sensitive (katp) and other potassium channels. methods: in the present study we applied intravital videomicroscopy to investigate the in situ effects of levosimendan and or-1896 on the diameters of real resistance arterioles (rat cremaster muscle arterioles with diameters of ~ 20 μm). results: levosimendan and or-1896 induced concentration-dependent (1 nm - 100 μm) dilations to similar extents in these arterioles (maximal dilation from 23 ± 2 to 33 ± 2 μm and from 22 ± 1 to 32 ± 1 μm,respectively). the arteriolar dilations induced by the selective katp channel opener pinacidil (1 nm - 10 μm) (maximal dilation from 22 ± 4 μm to 35 ± 3 μm) were diminished in the presence of the selective katp channel blocker - glibenclamide (5 μm) (maximal diameter attained: 22 ± 1 μm). glibenclamide also counteracted the maximal dilations in response to levosimendan or or-1896 (to 23 ± 3 μm or 22 ± 5 μm,respectively). conclusions: in conclusion,this is the first demonstration that levosimendan and or-1896 elicit arteriolar dilation in vivo,via activation of katp channels in real resistance vessels in the rat.copyright © 2013 by institute of pharmacology polish academy of sciences.