title: Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension.
abstract: Pulmonary hypertension (PH) is a rare disorder that without treatment is progressive and often fatal within 3 years. The treatment of PH involves the use of a diverse group of drugs and lung transplantation. Although nitrite was once thought to be an inactive metabolite of endothelial-derived nitric oxide (NO), there is increasing evidence that nitrite may be useful in the treatment of PH, but the mechanism by which nitrite exerts its beneficial effect remains uncertain. The purpose of this study was to investigate the effect of chronic sodium nitrite treatment in a PH model in the rat. Following induction of PH with a single injection of monocrotaline, 60 mg; daily ip injections of sodium nitrite (3mg/kg) starting on day 14 and continuing for 21 days, resulted in a significantly lower pulmonary arterial pressure on day 35 when compared to values in untreated animals with monocrotaline-induced PH. In monocrotaline-treated rats, daily treatment with ip nitrite injections for 21 days decreased right ventricular mass and pathologic changes in small pulmonary arteries. Nitrite therapy did not change systemic arterial pressure or cardiac output when values were measured on day 35. The decreases in pulmonary arterial pressure in response to iv injections of sodium nitroprusside, sodium nitrite, and BAY 41-8543 were not different in rats with monocrotaline-induced pulmonary hypertension and rats with chronic nitrite therapy when compared to responses in animals in which pulmonary arterial pressure was increased with U46619. These findings are consistent with the hypothesis that the mechanisms that convert nitrite to vasoactive NO, activate soluble guanylyl cyclase and mediate the vasodilator response to NO or an NO derivative are not impaired. The present data are consistent with the results of a previous study in monocrotaline-induced PH in which systemic arterial pressure and cardiac output were not evaluated and are consistent with the hypothesis that nitrite is effective in the treatment of monocrotaline-induced PH in the rodent.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Pankey
authors.forename: Adeleke M
authors.initials: AM
authors.lastname: Badejo
authors.forename: David B
authors.initials: DB
authors.lastname: Casey
authors.forename: George F
authors.initials: GF
authors.lastname: Lasker
authors.forename: Russel A
authors.initials: RA
authors.lastname: Riehl
authors.forename: Subramanyam N
authors.initials: SN
authors.lastname: Murthy
authors.forename: Bobby D
authors.initials: BD
authors.lastname: Nossaman
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy; D008168:Lung / Q000187:drug effects / Q000473:pathology; D016686:Monocrotaline; D009025:Morpholines; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside; D011743:Pyrimidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000494:pharmacology*; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology
chemical_list: C450679:BAY 41-8543; D009025:Morpholines; D011743:Pyrimidines; D009599:Nitroprusside; D009569:Nitric Oxide; D016686:Monocrotaline; D012977:Sodium Nitrite