l-Arginine attenuates acute pulmonary embolism-induced oxidative stress and pulmonary hypertension.
l-Arginine is substrate for nitric oxide (NO) synthesis and produces pulmonary vasodilatory effects in patients with pulmonary hypertension and in hypoxic animals. We hypothesized that l-arginine would attenuate the increase in oxidative stress and the pulmonary hypertension observed during acute pulmonary embolism (APE). Using an isolated lung perfusion rat model of APE, we examined whether l-arginine (0, 0.1, 0.5, 3, and 10 mmol/L) attenuates the pulmonary hypertension induced by the injection of 6.6 mg/kg of 300 microm Sephadex microspheres into the pulmonary artery. Thiobarbituric acid reactive species (TBA-RS) and nitrite/nitrate (NO(x)) concentrations were measured in lung perfusate to assess oxidative stress and NO production. l-Arginine (0.5, 3, and 10 mmol/L) attenuated (all P<0.05) APE-induced pulmonary hypertension by about 50%. The protective effect of l-arginine was completely reversed by inhibition of NO synthesis with l-NAME (4 mmol/L). In addition, l-arginine (0.5-10 mmol/L) blunted the increase in TBA-RS observed after APE. NO(x) tended to increase only when l-arginine (10 mmol/L) was added to the lung perfusate of non-embolized lungs. Taken together, these findings suggest that l-arginine attenuates APE-induced pulmonary hypertension through antioxidant mechanisms involving increased NO synthesis.
Souza-Costa
Debora Cristine
DC
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
Zerbini
Talita
T
Metzger
Ingrid Ferreira
IF
Rocha
João Batista Teixeira
JB
Gerlach
Raquel Fernanda
RF
Tanus-Santos
Jose Eduardo
JE
D000208:Acute Disease; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003911:Dextrans / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D003911:Dextrans; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; C025614:sephadex; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester