Chronic blockade of the angiotensin II receptor has a differential effect on adipose and vascular PAI-1 in OLETF rats.
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.
Kim
Myeung-Ju
MJ
Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chung-nam 330-714, South Korea.
Lee
Dae-Ho
DH
Park
Deok-Bae
DB
Kang
Hyun-Wook
HW
An
Chun-San
CS
Cui
Xiu-Ji
XJ
Kang
Jung-Sook
JS
Kim
Jung-Lye
JL
Lee
Young-Jae
YJ
Jung
Kee-Wook
KW
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
D057911:Angiotensin Receptor Antagonists; D017395:Plasminogen Activator Inhibitor 1; D011945:Receptors, Angiotensin; D014409:Tumor Necrosis Factor-alpha; D000808:Angiotensinogen; D019808:Losartan