a Department of Physiological Sciences , State University of Londrina , Londrina , Brazil.
b Department of Pathological Sciences , State University of Londrina , Londrina , Brazil.
Clin Exp Hypertens. 2017;39(1):50-57. doi: 10.1080/10641963.2016.1210628. Epub 2017 Jan 5.
It has been suggested that nitric oxide (NO) from iNOS source is involved in inflammation and oxidative stress, and hypertension in obese subjects involves an inflammatory process. However, no study evaluated the participation of iNOS inhibition on cardiovascular, autonomic, and inflammatory parameters in obese rats. Obesity was induced by the administration of 4 mg/g body weight of monosodium glutamate (MSG) or equimolar saline (CTR) in newborn rats. On the 60th day, treatment with aminoguanidine (Amino, 50 mg/kg), an iNOS inhibitor, or 0.9% saline, was started. On the 90th day, mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious rats and autonomic modulation was conducted with the CardioSeries software. Plasma samples were collected to assess lipid peroxidation and prostaglandins (PGE). In addition, iNOS immunohistochemistry in cardiac tissue was evaluated. MSG rats showed hypertension compared to CTR, and Amino treatment did not reverse it. Obese rats presented increased sympathetic and decreased parasympathetic modulation to the heart, reverted by Amino treatment. Plasma PGE was increased in obese rats, and Amino treatment decreased. Obese rats presented increased plasma lipoperoxidation, which was decreased after Amino treatment. Also, cardiac iNOS immunohistochemistry was decreased after Amino treatment. Our data suggest that iNOS activation is involved in the systemic and cardiac mechanisms of oxidative stress, inflammation, and autonomic dysfunction derived from obesity.
有人提出，诱导型一氧化氮合酶（iNOS）产生的一氧化氮（NO）与肥胖人群中的炎症和氧化应激以及高血压有关，而肥胖人群中涉及炎症过程。然而，尚无研究评估 iNOS 抑制剂对肥胖大鼠心血管、自主神经和炎症参数的影响。通过给新生大鼠施用 4mg/g 体重的谷氨酸单钠（MSG）或等摩尔生理盐水（CTR）来诱导肥胖。在第 60 天，开始用 iNOS 抑制剂氨基胍（Amino，50mg/kg）或 0.9%生理盐水进行治疗。在第 90 天，在清醒的大鼠中记录平均动脉压（MAP）和心率（HR），并使用 CardioSeries 软件进行自主神经调节。收集血浆样本以评估脂质过氧化和前列腺素（PGE）。此外，还评估了心脏组织中的 iNOS 免疫组织化学。与 CTR 相比，MSG 大鼠表现出高血压，而 Amino 治疗并未逆转这种情况。肥胖大鼠的心脏交感神经调节增加，副交感神经调节减少，而 Amino 治疗可逆转这种情况。肥胖大鼠的血浆 PGE 增加，而 Amino 治疗可降低。肥胖大鼠的血浆脂质过氧化增加，而 Amino 治疗后降低。此外，Amino 治疗后心脏 iNOS 免疫组织化学减少。我们的数据表明，iNOS 的激活参与了肥胖引起的系统性和心脏氧化应激、炎症和自主神经功能障碍的机制。
