title: Soluble guanylyl cyclase is reduced in airway smooth muscle cells from a murine model of allergic asthma.
abstract: Airway remodeling plays an important role in the development of airway hyperresponsiveness in asthma. Muscarinic agonists such as carbamylcholine increased cyclic GMP (cGMP) levels in bovine tracheal smooth muscle strips, via stimulation of NO-sensitive soluble guanylylcyclase (NO-sGC), which is an enzyme highly expressed in the lungs. cGMP production, by activation of a NO-sGC, may contribute to airway smooth muscle relaxation. To determine whether the bronchoconstriction observed in asthma is accompanied by changes in this NO-sGC activity, we used a well-established murine model, ovalbumin-airway smooth muscle cells (OVA-ASMCs) of allergic asthma to evaluate such hypothesis. Histologic studies of trachea specimens showed the existence of inflammation, hyperplasia and tissue remodeling in OVA-ASMCs. Interestingly, cultured OVA-ASMCs showed lower GC basal activity than CONTROL-ASMCs. Also, we found that both OVA-ASMCs and CONTROL cells exposed to carbamylcholine and sodium nitroprusside and combinations of both drugs increased cGMP levels, which were inhibited by 1H-[1,2,4]oxadiazolo[4,3-] quinoxalin-1-one. All the experimental evidence suggests that NO-sGC activity is reduced in isolated ASMCss from experimental asthma murine model.
authors.affiliation: From the Sección de Biomembranas, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Sabana Grande, Caracas, Venezuela.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Placeres-Uray
authors.forename: Ramona
authors.initials: R
authors.lastname: González de Alfonzo
authors.forename: Itala
authors.initials: I
authors.lastname: Lippo de Becemberg
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Alfonzo