Coelho Michella Soares, Lopes Karen Lucasechi, Freitas Raphael de Aquino, de Oliveira-Sales Elizabeth Barbosa, Bergasmaschi Cássia Toledo, Campos Ruy Ribeiro, Casarini Dulce Elena, Carmona Adriana Karaoglanovic, Araújo Mariana da Silva, Heimann Joel Claudio, Dolnikoff Miriam Sterman
Department of Internal Medicine, Laboratory of Experimental Hypertension of the University of São Paulo School of Medicine, Brazil.
Regul Pept. 2010 Jun 8;162(1-3):61-7. doi: 10.1016/j.regpep.2010.03.008. Epub 2010 Mar 24.
Sucrose-fed rats, a model of metabolic syndrome, are characterized by insulin resistance, obesity, hypertension, and high plasma levels of triacylglycerols and angiotensin II (Ang II). However, whether tissue renin-angiotensin system (RAS) is altered in metabolic syndrome is unclear. To study this issue, food ad libitum and water (C) or 20% sucrose solution (SC) were given to adult male Wistar rats, for 30 days. Body weight (BW), blood pressure (BP), epididymal adipose tissue (EPI) mass, rate of in vivo fatty acid (FA) synthesis in EPI, circulating glucose, insulin, leptin, angiotensins I and II, triacylglycerols, and plasma renin (PRA) and angiotensin-converting enzyme (ACE) activities were evaluated. In kidneys and EPI, gene and protein expression of type 1 (AT(1)) and 2 (AT(2)) Ang II receptors, ACE, angiotensinogen (AGT) as well as protein expression of angiotensin-converting enzyme 2 (ACE2) were determined. In both tissues, Ang I, Ang II and Ang-(1-7) contents were also measured by HPLC. In SC rats higher BP, EPI mass, circulating triacylglycerols, insulin, leptin, PRA and, Ang II were found. In EPI, the rate of in vivo FA synthesis was associated with increased Ang-(1-7), protein expression of AT(1) and AT(2) receptors, ACE2, AGT, and gene expression of AGT although a reduction in ACE activity and in adipose Ang I and Ang II contents was observed. In kidneys, AT(1) and AT(2), ACE and AGT gene and protein expression as well as protein expression of ACE2 were unaltered while Ang II, Ang-(1-7) and ACE activity increased. These RAS component changes seem to be tissue specific and possibly are related to enhancement of FA synthesis, EPI mass and hypertension.
以蔗糖喂养的大鼠是代谢综合征的一种模型，其特征为胰岛素抵抗、肥胖、高血压以及血浆中甘油三酯和血管紧张素II（Ang II）水平升高。然而，代谢综合征中组织肾素 - 血管紧张素系统（RAS）是否发生改变尚不清楚。为研究此问题，给成年雄性Wistar大鼠随意喂食食物和水（C组）或20%蔗糖溶液（SC组），持续30天。评估体重（BW）、血压（BP）、附睾脂肪组织（EPI）质量、EPI中体内脂肪酸（FA）合成速率、循环葡萄糖、胰岛素、瘦素、血管紧张素I和II、甘油三酯以及血浆肾素（PRA）和血管紧张素转换酶（ACE）活性。测定肾脏和EPI中1型（AT(1)）和2型（AT(2)）Ang II受体、ACE、血管紧张素原（AGT）的基因和蛋白表达以及血管紧张素转换酶2（ACE2）的蛋白表达。在这两种组织中，还通过高效液相色谱法测量Ang I、Ang II和Ang-(1 - 7)含量。在SC组大鼠中，发现血压、EPI质量、循环甘油三酯、胰岛素、瘦素、PRA和Ang II升高。在EPI中，体内FA合成速率与Ang-(1 - 7)增加、AT(1)和AT(2)受体、ACE2、AGT的蛋白表达以及AGT的基因表达相关，尽管观察到ACE活性以及脂肪组织中Ang I和Ang II含量降低。在肾脏中，AT(1)和AT(2)、ACE和AGT的基因和蛋白表达以及ACE2的蛋白表达未改变，而Ang II、Ang-(1 - 7)和ACE活性增加。这些RAS组分变化似乎具有组织特异性，并且可能与FA合成增强、EPI质量增加和高血压有关。
