Azhar A, El-Bassossy H M
Department of Pediatric Cardiology, Faculty of Medicine, King Abdulaziz University, P. O. Box 80260, Jeddah, 21589, Kingdom of Saudi Arabia.
Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
J Endocrinol Invest. 2015 Apr;38(4):437-45. doi: 10.1007/s40618-014-0209-z. Epub 2014 Nov 21.
Pentoxifylline is a well-tolerated drug used in treatment of vascular insufficiency. We previously showed that pentoxifylline protects from impairment in vascular reactivity in cases of metabolic syndrome. The aim of this study was to investigate the protective effect of pentoxifylline against hypertension in metabolic syndrome rats.
Metabolic syndrome was induced by feeding rats a high-fructose, high-fat and high-salt diet for 12 weeks. Pentoxifylline was administered daily (30 mg kg(-1)) during the last 4 weeks of the study, before blood pressure parameters were assessed at the end of study. In addition, serum levels of glucose, fructosamine, insulin, tumor necrosis factor alpha, adiponectin, and lipid profile parameters were determined. Aortic protein levels of angiotensin II and angiotensin receptor 1 were assessed by immunofluorescence.
Pentoxifylline administration prevented excessive weight gain but did not affect hyperinsulinemia or hypertriglyceridemia seen in metabolic syndrome animals. In addition, pentoxifylline prevented the elevations in mean blood pressure associated with metabolic syndrome. Particularly, pentoxifylline prevented elevations in systolic, diastolic, and notch blood pressure; however, elevation in pulse blood pressure was not affected. Further, pentoxifylline alleviated the low-grade inflammation associated with metabolic syndrome, as reflected by the significantly lower serum tumor necrosis factor α and higher serum adiponectin levels metabolic syndrome animals treated with pentoxifylline. Also, pentoxifylline inhibited elevated expression of angiotensin receptor 1 in aortic tissue of metabolic syndrome animals.
Pentoxifylline directly alleviated hypertension in metabolic syndrome rats, at least in part, via amelioration of low-grade inflammation and inhibition of angiotensin system.
己酮可可碱是一种耐受性良好的用于治疗血管功能不全的药物。我们之前表明,己酮可可碱可保护代谢综合征患者的血管反应性免受损害。本研究的目的是探讨己酮可可碱对代谢综合征大鼠高血压的保护作用。
通过给大鼠喂食高果糖、高脂肪和高盐饮食12周诱导代谢综合征。在研究的最后4周每天给予己酮可可碱(30 mg kg⁻¹),在研究结束时评估血压参数之前。此外,测定血清葡萄糖、果糖胺、胰岛素、肿瘤坏死因子α、脂联素水平以及血脂参数。通过免疫荧光评估主动脉中血管紧张素II和血管紧张素受体1的蛋白水平。
给予己酮可可碱可防止体重过度增加,但不影响代谢综合征动物出现的高胰岛素血症或高甘油三酯血症。此外,己酮可可碱可防止与代谢综合征相关的平均血压升高。特别是,己酮可可碱可防止收缩压、舒张压和脉压升高;然而,脉压差升高不受影响。此外,己酮可可碱减轻了与代谢综合征相关的低度炎症,这表现为己酮可可碱治疗的代谢综合征动物血清肿瘤坏死因子α显著降低和血清脂联素水平升高。而且,己酮可可碱抑制了代谢综合征动物主动脉组织中血管紧张素受体1的表达升高。
己酮可可碱至少部分通过改善低度炎症和抑制血管紧张素系统直接减轻代谢综合征大鼠的高血压。