title: Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo.
abstract: 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.
authors.affiliation: Division of Clinical Physiology, Institute of Cardiology, Medical and Health Science Center, University of Debrecen, Móricz Zs. krt. 22, H-4032 Debrecen, Hungary. pappz@med.unideb.hu.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Gödény
authors.forename: Piero
authors.initials: P
authors.lastname: Pollesello
authors.forename: István
authors.initials: I
authors.lastname: Edes
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Papp
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bagi
mesh_terms: D000081:Acetamides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006835:Hydrazones / Q000378:metabolism / Q000494:pharmacology*; D054086:KATP Channels / Q000819:agonists* / Q000378:metabolism; D008297:Male; D018715:Microscopy, Video; D009130:Muscle, Smooth / Q000098:blood supply*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011724:Pyridazines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077464:Simendan; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D006835:Hydrazones; D054086:KATP Channels; C414222:N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide; D026902:Potassium Channel Blockers; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan