title: Treatment with LA-419 prevents monocrotaline-induced pulmonary hypertension and lung injury in the rat.
abstract: We evaluated the therapeutic potential of LA-419, a hybrid organic nitrate that donates nitric oxide and thiol groups, to improve pulmonary arterial hypertension in an experimental model induced by monocrotaline in the rat. Treatment with LA-419 from the first day after monocrotaline administration prevented the increase in pulmonary pressure as well as the increases in ventricle/body weight and pulmonary artery wall thickness. Administration of LA-419 after establishment of hypertensive status also resulted in an improvement of these parameters. Both preventive and therapeutic treatments reduced mortality. The antioxidant effect of LA-419 was comparable to that achieved with a-tocopherol. Pulmonary remodeling accomplished by LA-419 could be attributed to a balanced antioxidant effect associated with its nitric oxide/SH donor capability. Thus, LA-419 might represent a new therapeutic approach in severe pulmonary hypertension in humans.
authors.affiliation: Research and Development Department, Pharmaceutical Division, Lacer S A, Barcelona, Spain. marisabel.mourelle@lacer.es
authors.forename: M
authors.initials: M
authors.lastname: Mourelle
authors.forename: M T
authors.initials: MT
authors.lastname: Martin
authors.forename: F
authors.initials: F
authors.lastname: Giménez
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000517:prevention & control*; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C503157:LA 419; D020030:Nitric Oxide Donors; D016686:Monocrotaline; D007548:Isosorbide Dinitrate