title: The influence of ruthenium on vascular tone.
abstract: OBJECTIVE
  Over the past few years, ruthenium has been under attention for development of organometallic drugs with various therapeutic applications. Because of its favourable characteristics, ruthenium is perfectly suitable for drug design. Ruthenium-containing complexes exert a wide range of biological effects. However, so far, the influence of ruthenium itself on vascular tone has never been studied.
  
  
  METHODS
  The effect of ruthenium was analysed through organ bath studies measuring isometric tension on mice thoracic aorta. After obtaining a stable contraction plateau, cumulative concentration-response curves of the ruthenium-compounds (RuCl3 , Ruthenium Red, [RuCl2 (CO)3 ]2 and RuCl2 (DMSO)4 ) (30-600 μmol/l) were performed. The effect of RuCl3 after contraction with different contractile agents was evaluated. Furthermore, the influence of ruthenium-containing molecules on endogenous (acetylcholine) and exogenous (sodium nitroprusside) NO-mediated relaxations was determined.
  
  
  RESULTS
  All studied ruthenium compounds elicit, to some extent, a decrease of the contraction level. Looking further into the underlying mechanism, we found that RuCl3 relaxes aortic rings only when contracted with norepinephrine. This RuCl3 -induced relaxation can be prevented by the antioxidants ascorbic acid and N-acetyl L-cysteine. In addition, ruthenium compounds may diminish acetylcholine- or sodium nitroprusside-induced relaxations.
  
  
  CONCLUSIONS
  Ruthenium-containing molecules can influence vascular tone induced by norepinephrine due to oxidative inactivation. Moreover, they can undermine NO-mediated responses. This should be considered when developing ruthenium-containing drugs.
authors: Department of Pharmacology, Ghent University, Ghent, Belgium.
authors: Bart
authors: B
authors: Pauwels
authors: Department of Pharmacology, Ghent University, Ghent, Belgium.
authors: Charlotte
authors: C
authors: Boydens
authors: Department of Pharmacology, Ghent University, Ghent, Belgium.
authors: Johan
authors: J
authors: Van de Voorde
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D012428:Ruthenium / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D012428:Ruthenium; D003545:Cysteine; D000109:Acetylcholine; D009638:Norepinephrine
keywords: aorta; ascorbic acid; carbon monoxide-releasing molecule; nitric oxide; ruthenium