title: Vascular response of ruthenium tetraamines in aortic ring from normotensive rats.
abstract: BACKGROUND
  Ruthenium (Ru) tetraamines are being increasingly used as nitric oxide (NO) carriers. In this context, pharmacological studies have become highly relevant to better understand the mechanism of action involved.
  
  
  OBJECTIVE
  To evaluate the vascular response of the tetraamines trans-[Ru(II)(NH3)4(Py)(NO)](3+), trans-[Ru(II)(Cl)(NO) (cyclan)](PF6)2, and trans-[Ru(II)(NH3)4(4-acPy)(NO)](3+).
  
  
  METHODS
  Aortic rings were contracted with noradrenaline (10(-6) M). After voltage stabilization, a single concentration (10(-6) M) of the compounds was added to the assay medium. The responses were recorded during 120 min. Vascular integrity was assessed functionally using acetylcholine at 10(-6) M and sodium nitroprusside at 10(-6) M as well as by histological examination.
  
  
  RESULTS
  Histological analysis confirmed the presence or absence of endothelial cells in those tissues. All tetraamine complexes altered the contractile response induced by norepinephrine, resulting in increased tone followed by relaxation. In rings with endothelium, the inhibition of endothelial NO caused a reduction of the contractile effect caused by pyridine NO. No significant responses were observed in rings with endothelium after treatment with cyclan NO. In contrast, in rings without endothelium, the inhibition of guanylate cyclase significantly reduced the contractile response caused by the pyridine NO and cyclan NO complexes, and both complexes caused a relaxing effect.
  
  
  CONCLUSIONS
  The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10(-6) M) at the end of the incubation period in aortic rings with and without endothelium, indicating the slow release of NO from these complexes and suggesting that the ligands promoted chemical stability to the molecule. Moreover, we demonstrated that the association of Ru with NO is more stable when the ligands pyridine and cyclan are used in the formulation of the compound.
authors.affiliation: Universidade Estadual de Campinas, São Paulo, SP, Brasil.
authors.forename: Ana Gabriela
authors.initials: AG
authors.lastname: Conceição-Vertamatti
authors.affiliation: Universidade Estadual de Campinas, São Paulo, SP, Brasil.
authors.forename: Luiz Alberto Ferreira
authors.initials: LA
authors.lastname: Ramos
authors.affiliation: Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Ivy
authors.initials: I
authors.lastname: Calandreli
authors.affiliation: Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Aline Nunes
authors.initials: AN
authors.lastname: Chiba
authors.affiliation: Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Douglas Wagner
authors.initials: DW
authors.lastname: Franco
authors.affiliation: Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Elia
authors.initials: E
authors.lastname: Tfouni
authors.affiliation: Universidade Estadual de Campinas, São Paulo, SP, Brasil.
authors.forename: Dora Maria
authors.initials: DM
authors.lastname: Grassi-Kassisse
mesh_terms: D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000032:analysis; D009569:Nitric Oxide / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012428:Ruthenium / Q000494:pharmacology*; D017975:Ruthenium Compounds / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000588:Amines; D011725:Pyridines; D017975:Ruthenium Compounds; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D012428:Ruthenium; C023666:pyridine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine