Rubio-Ruiz María Esther, Pérez-Torres Israel, Diaz-Diaz Eulises, Pavón Natalia, Guarner-Lans Verónica
Departments of Physiology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
Departments of Pathology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
Acta Pharmacol Sin. 2014 Nov;35(11):1364-74. doi: 10.1038/aps.2014.67. Epub 2014 Sep 29.
Metabolic syndrome (MS) and aging are low-grade systemic inflammatory conditions, and inflammation is a key component of endothelial dysfunction. The aim of this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) upon the vascular reactivity in aging MS rats.
MS was induced in young male rats by adding 30% sucrose in drinking water over 6, 12, and 18 months. When the treatment was finished, the blood samples were collected, and aortas were dissected out. The expression of COX isoenzymes and PLA2 in the aortas was analyzed using Western blot analysis. The contractile responses of aortic rings to norepinephrine (1 μmol/L) were measured in the presence or absence of different NSAIDs (10 μmol/L for each).
Serum levels of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) in control rats were remained stable during the aging process, whereas serum IL-6 in MS rats were significantly increased at 12 and 18 months. The levels of COX isoenzyme and PLA2 in aortas from control rats increased with the aging, whereas those in aortas from MS rats were irregularly increased with the highest levels at 6 months. Pretreatment with acetylsalicylic acid (a COX-1 preferential inhibitor), indomethacin (a non-selective COX inhibitor) or meloxicam (a COX-2 preferential inhibitor) decreased NE-induced contractions of aortic rings from MS rats at all the ages, with meloxicam being the most potent. Acetylsalicylic acid also significantly reduced the maximum responses of ACh-induced vasorelaxation of aortic rings from MS rats, but indomethacin and meloxicam had no effect.
NSAIDs can directly affect vascular responses in aging MS rats. Understanding the effects of NSAIDs on blood vessels may improve the treatment of cardiovascular diseases and MS in the elders.
代谢综合征（MS）和衰老均为低度全身性炎症状态，且炎症是内皮功能障碍的关键组成部分。本研究旨在探讨非甾体抗炎药（NSAIDs）对衰老MS大鼠血管反应性的影响。
通过在6、12和18个月期间给年轻雄性大鼠饮用含30%蔗糖的水来诱导MS。治疗结束后，采集血样，并取出主动脉。采用蛋白质印迹分析检测主动脉中COX同工酶和PLA2的表达。在存在或不存在不同NSAIDs（每种10 μmol/L）的情况下，测量主动脉环对去甲肾上腺素（1 μmol/L）的收缩反应。
对照大鼠血清促炎细胞因子（IL-6、TNF-α和IL-1β）水平在衰老过程中保持稳定，而MS大鼠血清IL-6在12个月和18个月时显著升高。对照大鼠主动脉中COX同工酶和PLA2水平随衰老而升高，而MS大鼠主动脉中的水平则不规则升高，在6个月时达到最高。用乙酰水杨酸（一种COX-1选择性抑制剂）、吲哚美辛（一种非选择性COX抑制剂）或美洛昔康（一种COX-2选择性抑制剂）预处理可降低各年龄段MS大鼠主动脉环对NE诱导的收缩，其中美洛昔康作用最强。乙酰水杨酸还显著降低了MS大鼠主动脉环对ACh诱导的血管舒张的最大反应，但吲哚美辛和美洛昔康无此作用。
NSAIDs可直接影响衰老MS大鼠的血管反应。了解NSAIDs对血管的影响可能会改善老年人心血管疾病和MS的治疗。
