The influence of ruthenium on vascular tone.
OBJECTIVES
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.


KEY FINDINGS
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.
['Pauwels|Bart|B|', 'Boydens|Charlotte|C|', 'Van de Voorde|Johan|J|']
D000109:Acetylcholine D000818:Animals D001013:Aorta, Thoracic D003545:Cysteine D004730:Endothelium, Vascular D008297:Male D051379:Mice D009119:Muscle Contraction D009126:Muscle Relaxation D009131:Muscle, Smooth, Vascular D009569:Nitric Oxide D009599:Nitroprusside D009638:Norepinephrine D012428:Ruthenium D014664:Vasodilation
ruthenium aorta ascorbic acid carbon monoxide-releasing molecule nitric oxide