title: Relaxing effect of a new ruthenium complex nitric oxide donor on airway smooth muscle of an experimental model of asthma in rats.
abstract: NO is a potent bronchodilator and NO-donor compounds have demonstrated clinical significance for obstructive airway diseases. This study evaluated the relaxation mechanisms of two NO donors, a ruthenium compound (TERPY), and sodium nitroprusside (SNP), in rat tracheas with ovalbumin-induced asthma (OVA group) and in another control group. The effect of TERPY and SNP was evaluated in tracheal rings in an isolated organ chamber. The contribution of K(+) channels, sGC/cGMP pathway, phosphodiesterases, and extra and intracellular Ca(2+) sources were analyzed. The TERPY and SNP-induced tracheal smooth muscle relaxation in both groups. However, the maximum effect induced by TERPY was higher than that of SNP in both control (110.2 ± 3.2% vs 68.3 ± 3.1%, P < 0.001) and OVA groups (106.1 ± 1.5% vs 49.9 ± 2.7%, P < 0.001). In the control group, TERPY relaxation was induced by the activation of K(+) channels and reduction of the calcium influx, while in the OVA group, these same effects were also brought about by TERPY, but with participation of the sGC/cGMP pathway. In both groups, SNP-induced relaxation occurred through the activation of K(+) channels, sGC/cGMP pathway and reduction of calcium influx. However, the activation of sGC pathway and reticular Ca(2+) -ATPase seemed to be reduced in the OVA group. Furthermore, TERPY is capable of reversing the contraction of carbachol in asthmatic bronchioles. Finally, TERPY and SNP relaxation mechanisms were modified by asthma. SNP presented less relaxation than TERPY, which induced full relaxation with greater participation of K(+) and Ca(2+) fluxes through the membrane, thereby making TERPY a promising drug for reversing the narrowing of airways.
authors.affiliation: Faculty of Pharmacy, Federal University of Goias, Goiânia, GO, Brazil.
authors.forename: Patrícia Ferreira da Silva
authors.initials: PF
authors.lastname: Castro
authors.affiliation: Faculty of Pharmacy, Federal University of Goias, Goiânia, GO, Brazil.
authors.forename: Daniela Lobo
authors.initials: DL
authors.lastname: de Andrade
authors.affiliation: Faculty of Pharmacy, Federal University of Goias, Goiânia, GO, Brazil.
authors.forename: Carolina de Fátima
authors.initials: Cde F
authors.lastname: Reis
authors.affiliation: Faculty of Pharmacy, Federal University of Goias, Goiânia, GO, Brazil.
authors.forename: Sérgio Henrique Nascente
authors.initials: SH
authors.lastname: Costa
authors.affiliation: Faculty of Odontology, Federal University of Goias, Goiânia, GO, Brazil.
authors.forename: Aline Carvalho
authors.initials: AC
authors.lastname: Batista
authors.affiliation: Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Roberto Santana
authors.initials: RS
authors.lastname: da Silva
authors.affiliation: Faculty of Pharmacy, Federal University of Goias, Goiânia, GO, Brazil.
authors.forename: Matheus Lavorenti
authors.initials: ML
authors.lastname: Rocha
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology*; D020030:Nitric Oxide Donors / Q000737:chemistry*; D009599:Nitroprusside / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D000071756:Soluble Guanylyl Cyclase; D014132:Trachea / Q000187:drug effects
chemical_list: D020030:Nitric Oxide Donors; D009942:Organometallic Compounds; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D018160:Receptors, Cytoplasmic and Nuclear; D009599:Nitroprusside; D012428:Ruthenium; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D002118:Calcium
keywords: K+ channels; airway smooth muscle; asthma; nitric oxide; ruthenium complex