title: Identification of mechanisms involved in the relaxation of rabbit cavernous smooth muscle by a new nitric oxide donor ruthenium compound.
abstract: OBJECTIVE
  The aim of this study was to evaluate the relaxation in vitro of cavernous smooth muscle induced by a new NO donor of the complex nitrosil-ruthenium, named trans-[Ru(NH3)4(caffeine)(NO)]C13 (Rut-Caf) and sodium nitroprusside (SNP).
  
  
  METHODS
  The tissues, immersed in isolated bath systems, were pre-contracted with phenilephrine (PE) (1 µM) and then concentration-response curves (10 (-12) - 10(-4) M) were obtained. To clarify the mechanism of action involved, it was added to the baths ODQ (10 µM, 30 µM), oxyhemoglobin (10 µM), L-cysteine (100 µM), hydroxicobalamine (100 µM), glibenclamide, iberotoxin and apamine. Tissue samples were frozen in liquid nitrogen to measure the amount of cGMP and cAMP produced.
  
  
  RESULTS
  The substances provoked significant relaxation of the cavernous smooth muscle. Both Rut-Caf and SNP determined dose-dependent relaxation with similar potency (pEC50) and maximum effect (E(max)). The substances showed activity through activation of the soluble guanylyl cyclase (sGC), because the relaxations were inhibited by ODQ. Oxyhemoglobin significantly diminished the relaxation effect of the substances. L-cysteine failed to modify the relaxations caused by the agents. Hydroxicobalamine significantly diminished the relaxation effect of Rut-Caf. Glibenclamide significantly increased the efficacy of Rut-Caf (pEC50 4.09 x 7.09). There were no alterations of potency or maximum effect of the substances with the addition of the other ion channel blockers. Rut-Caf induced production of significant amounts of cGMP and cAMP during the relaxation process.
  
  
  CONCLUSIONS
  In conclusion, Rut-Caf causes relaxation of smooth muscle of corpus cavernosum by means of activation of sGC with intracellular production of cGMP and cAMP; and also by release of NO in the intracellular environment. Rut-Caf releases the NO free radical and it does not act directly on the potassium ion channels.
authors.affiliation: Departamento de Cirurgia, Universidade Federal do Ceará, Ceará, Brazil. joaogadelhac@gmail.com
authors.forename: João Batista Gadelha de
authors.initials: JB
authors.lastname: Cerqueira
authors.forename: Lucio Flávio
authors.initials: LF
authors.lastname: Gonzaga-Silva
authors.forename: Francisco Ordelei Nascimento da
authors.initials: FO
authors.lastname: Silva
authors.forename: João Victor Medeiros de
authors.initials: JV
authors.lastname: Cerqueira
authors.forename: Ricardo Reges Maia
authors.initials: RR
authors.lastname: Oliveira
authors.forename: Maria Elisabete Amaral de
authors.initials: ME
authors.lastname: Moraes
authors.forename: Nilberto Robson Falcão do
authors.initials: NR
authors.lastname: Nascimento
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis / Q000737:chemistry; D003545:Cysteine / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000096:biosynthesis / Q000737:chemistry; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology*; D009599:Nitroprusside / Q000737:chemistry / Q000494:pharmacology*; D015221:Potassium Channels / Q000737:chemistry; D011817:Rabbits; D017975:Ruthenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D020030:Nitric Oxide Donors; D015221:Potassium Channels; D017975:Ruthenium Compounds; D009599:Nitroprusside; D006157:Guanosine Monophosphate; D006152:Cyclic GMP; D003545:Cysteine