Oxidative stress in the infarcted heart: role of de novo angiotensin II production.
This study aimed to elucidate whether angiotensin (Ang) II generated de novo at the infarct site regulates the redox state of inflammatory cells participating in cardiac repair. On days 3-28 following ligation of the rat left coronary artery, we addressed at the infarct site: (a) the appearance and cellular origin of oxidative stress by monitoring the expression (mRNA and protein) of gp91phox (a subunit of superoxide producing NADPH oxidase) and the antioxidant superoxide dismutase (SOD), together with the presence of 3-nitrotyrosine (a marker of oxidative stress); (b) the presence of components requisite to Ang peptide generation; and (c) response to treatment with losartan (Los, 10mg/kg/day). We found at the infarct site, macrophage-derived oxidative stress appears during week 1 coincident with the appearance of components requisite to AngII generation and activity in these cells. Based on observed response to AT1 receptor antagonism with Los, we would suggest de novo AngII, in an autocrine manner, participates in the induction of oxidative stress while suppressing the expression of antioxidant defenses.
Lu
Li
L
Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
Quinn
Mark T
MT
Sun
Yao
Y
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism*; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014018:Tissue Distribution; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D019808:Losartan