Kim Myeung-Ju, Lee Dae-Ho, Park Deok-Bae, Kang Hyun-Wook, An Chun-San, Cui Xiu-Ji, Kang Jung-Sook, Kim Jung-Lye, Lee Young-Jae, Jung Kee-Wook
Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chung-nam 330-714, South Korea.
Diabetes Res Clin Pract. 2006 Jul;73(1):8-16. doi: 10.1016/j.diabres.2005.11.013. Epub 2006 Jan 18.
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.
血管紧张素原（AGT）和纤溶酶原激活物抑制剂-1（PAI-1）在血管组织和脂肪组织中均有表达。血管紧张素II（AG II）具有促脂肪生成作用，并可增加PAI-1的表达。为评估1型血管紧张素II受体（AT(1)R）拮抗剂对2型糖尿病模型大冢长- Evans德岛肥胖（OLETF）大鼠脂肪量及血管和脂肪组织中PAI-1表达的慢性影响，给予OLETF大鼠氯沙坦（30mg/kg/天），持续20周。在OLETF大鼠中，慢性AT(1)R拮抗后，腹部脂肪量和局部脂肪分布未发生变化。与正常对照大冢长- Evans德岛（LETO）大鼠相比，OLETF大鼠脂肪组织中AGT和PAI-1 mRNA表达显著增加。慢性氯沙坦治疗进一步提高了OLETF大鼠脂肪组织中AGT的水平，但不影响脂肪组织PAI-1 mRNA的水平。相反，慢性氯沙坦治疗可使OLETF大鼠主动脉PAI-1表达减弱。我们的研究结果有两点意义。第一，即使经过慢性氯沙坦治疗，脂肪组织仍可能是代谢综合征中AG II的重要来源。第二，氯沙坦慢性拮抗AT(1)R对血管和脂肪组织中PAI-1的表达产生不同影响。
