Hypotensive properties and acute toxicity of trans-[Ru(NH(3))(4)P(OEt)(3)(NO)](PF(6))(3), a new nitric oxide donor.
The hypotensive effect and the acute toxicity of trans-[Ru(NH(3))(4)P(OEt)(3)(NO)](PF(6))(3) (RuNO) were investigated in conscious animals. The approximate lethal dose of RuNO is 257.5 micromol/kg in mice i.p. and the IC(50) 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)] (SNP) 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.
Torsoni
Adriana Souza
AS
Departamento de Fisiologia e Biofísica, Universidade Estadual de Campinas, Campinas, SP, Brazil.
de Barros
Brígida Figueiredo
BF
Toledo
José Carlos
JC
Haun
Marcela
M
Krieger
Marta Helena
MH
Tfouni
Elia
E
Franco
Douglas Wagner
DW
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D006224:Cricetinae; D051379:Mice; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000633:toxicity*; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012428:Ruthenium / Q000494:pharmacology*
D000959:Antihypertensive Agents; D020030:Nitric Oxide Donors; D009942:Organometallic Compounds; D012428:Ruthenium