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

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.