Hypotensive properties and acute toxicity of trans-[Ru(NH3)4P(OEt)3(NO)](PF6)3, a new nitric oxide donor

The hypotensive effect and the acute toxicity of trans-[Ru(NH3)(4)P(OEt)(3)(NO)](PF6)(3) (RuNO) were investigated in conscious animals. The approximate lethal dose of RuNO is 257.5 mumol/kg in mice i.p. and the IC50 values evaluated for V79 culture cell cytotoxicity were higher than 2.0 mM, suggesting that the ruthenium species are significantly less toxic than Na-2[Fe(CN)(5)(NO)] (SN-P) species. The RuNO hypotensive effect measured through in-bolus intravenous administration in chronically instrumented normotensive and hypotensive adult male Wistar rats is similar to that exhibited by equivalent doses of SNP. The hypotensive effect of the ruthenium complex is fully inhibited by methylene blue and PTIO, suggesting that the RuNO effect is likely to be primarily dependent on the NO-[cGMP] pathway in the smooth muscle cells. (C) 2002 Elsevier Science (USA).