title: Chronic blockade of the angiotensin II receptor has a differential effect on adipose and vascular PAI-1 in OLETF rats.
abstract: Angiotensinogen (AGT) and plasminogen activator inhibitor-1 (PAI-1) are expressed in both vascular and adipose tissues. Angiotensin II (AG II) has an adipogenic effect and increases PAI-1 expression. To evaluate the chronic effects of AG II type 1 receptor (AT(1)R) antagonism on adipose mass and PAI-1 expression in vascular and adipose tissues, losartan (30mg/kg/day) was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes, for 20 weeks. Adipose mass and regional fat distribution in the abdomen did not change after chronic AT(1)R antagonism in OLETF rats. AGT and PAI-1 mRNA expressions in adipose tissue of OLETF rats were significantly increased compared with Long-Evans Tokushima Otsuka (LETO) rats, the normal control. Chronic losartan therapy further increased the level of adipose AGT in OLETF rats, but did not affect the level of adipose PAI-1 mRNA. In contrast, aortic PAI-1 expression in OLETF rats was attenuated by chronic losartan therapy. Our results have two implications. First, adipose tissue may be an important source of AG II in metabolic syndrome even after chronic losartan therapy. Second, chronic AT(1)R antagonism with losartan causes differential effects on vascular and adipose PAI-1 expression.
authors.affiliation: Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chung-nam 330-714, South Korea.
authors.forename: Myeung-Ju
authors.initials: MJ
authors.lastname: Kim
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Deok-Bae
authors.initials: DB
authors.lastname: Park
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Kang
authors.forename: Chun-San
authors.initials: CS
authors.lastname: An
authors.forename: Xiu-Ji
authors.initials: XJ
authors.lastname: Cui
authors.forename: Jung-Sook
authors.initials: JS
authors.lastname: Kang
authors.forename: Jung-Lye
authors.initials: JL
authors.lastname: Kim
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Lee
authors.forename: Kee-Wook
authors.initials: KW
authors.lastname: Jung
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000503:physiopathology; D057911:Angiotensin Receptor Antagonists; D000808:Angiotensinogen / Q000096:biosynthesis; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008643:Mesentery / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D020334:Rats, Inbred OLETF; D011945:Receptors, Angiotensin / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D057911:Angiotensin Receptor Antagonists; D017395:Plasminogen Activator Inhibitor 1; D011945:Receptors, Angiotensin; D014409:Tumor Necrosis Factor-alpha; D000808:Angiotensinogen; D019808:Losartan