title: Role of new agents affecting NO/cGMP pathway on ovalbumin-sensitized guinea pig trachea.
abstract: Asthma is a chronic inflammatory disease in which cell components play important roles. We aimed to evaluate the effects of NO/cGMP cleavage at trachea preparations isolated from ovalbumin-sensitized guinea pigs in vitro. Trachea rings were exposed to 3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC-12), (±)-(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexen-1-yl-nicotinamide (NOR-4), 2-(2-methylpyridin-4-yl)methyl-4-(3,4,5-trimethoxyphenyl)-8-(pyrimidin-2-yl) methoxy-1,2-dihydro-1-oxo-2,7-naphthyridine-3-carboxylic acid methyl ester hydrochloride (T-0156), and electrical field stimulation (EFS). cGMP levels in trachea tissues were also measured. The relaxation responses of NOC-12, NOR-4, T-0156, and EFS were significantly decreased at ovalbumin-sensitized group. Nitric oxide (NO) donors significantly decreased the relaxation responses in the presence of 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ). L-Nitro-Arginine Methyl Ester (L-NAME) significantly decreased the EFS relaxation responses in both groups (experimental group and control group), but this effect was reversed by L-Arginine addition. In the experimental group, cGMP levels after EFS, carbachol, NOC-12, NOR-4, and T-0156 exposure were significantly lower than control group. In both groups, cGMP levels after NO donors' exposure were significantly lower in the presence of ODQ and the cGMP levels after EFS + L-NAME were significantly lower than EFS alone. These results may show the increased formation of NO because of the increased iNOS activity in airway sensitization leading to the inhibition of cNOS resulting in the decrease of endogen NO and decrease of activation of guanylyl cyclase.
authors.affiliation: Department of Pharmacy, Okmeydani Training and Research Hospital, Istanbul, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Parlak
authors.forename: Sahin
authors.initials: S
authors.lastname: Yildirim
authors.forename: Ihsan
authors.initials: I
authors.lastname: Bagcivan
authors.forename: Nedim
authors.initials: N
authors.lastname: Durmus
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000276:immunology; D009287:Naphthyridines / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
chemical_list: D001993:Bronchodilator Agents; C118603:NOC 12; C102260:NOR 4; D009287:Naphthyridines; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D011725:Pyridines; D011743:Pyrimidines; C473961:T0156; D009569:Nitric Oxide; D010047:Ovalbumin; D006152:Cyclic GMP