Chronic Losartan Therapy in OLETF Rats Has a Differential Effect on Adipose and Vascular PAM

Lee, Dae-Ho; Park, Deok-Bae; Lee, Young-Ki; Kang, Hyun-Wook

doi:2005.3.1.27

J Med Life Sci > Volume 3(1); 2005 > Article

Original Article

Journal of Medicine and Life Science 2005;3(1):27-37.
DOI: https://doi.org/10.22730/jmls.2005.3.1.27 Published online June 30, 2005.

Chronic Losartan Therapy in OLETF Rats Has a Differential Effect on Adipose and Vascular PAM

Dae-Ho Lee¹, Deok-Bae Park², Young-Ki Lee², Hyun-Wook Kang³

¹Department of Internal Medicine, College of Medicine, Cheju National University, Jeju 690-756, Korea.
²Department of Histology, College of Medicine, Cheju National University, Jeju 690-756, Korea.
³Department of Forensic Medicine, College of Medicine, Cheju National University, Jeju 690-756, Korea.

Correspondence: Dae-Ho Lee, Email: Ldhkso@cheju.ac.kr

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 (AT₁R) antagonism on adipose mass and PAI-1 expression in vascular and adipose tissues, losartan (30 mg/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 AT₁R 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 protein expression, assessed by immunofluorescent staining, was attenuated by chronic losartan therapy. Our results have three implications. First, chronic AT₁R antagonism with losartan increases AGT expression in adipose tissue; increased AGT may sustain PAI-1 expression in adipose tissue despite the AT₁R blockade. Second, chronic losartan therapy does not affect adipose mass. Third, chronic AT₁R antagonism with losartan has a differential effect on vascular and adipose PAI-1 expression.

Key Words: Plasminogen activator inhibitor-1, Angiotensinogen, OLETF rats, Type 2 diabetes; Losartan