Melatonin reverses the loss of the anticontractile effect of perivascular adipose tissue in obese rats
Melatonin reverses the loss of the anticontractile effect of perivascular adipose tissue in obese rats
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DOI：
10.1111/jpi.12710
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发表时间：
2020-12-26
影响因子：
10.3
通讯作者：
Tirapelli, Carlos R.
中科院分区：
文献类型：
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作者：
Gonzaga, Natalia A.;Awata, Wanessa M. C.;Tirapelli, Carlos R.
血管周围脂肪组织（PVAT）在肥胖症中发生功能性变化。增加的氧化应激是肥胖诱导PVAT的抗收缩作用丧失的中心机制。褪黑激素是一种抗氧化剂，在心血管疾病中显示血管保护作用。在这里，我们试图研究褪黑激素是否会恢复肥胖患者主动脉周围PVAT的抗收缩作用。雄性Wistar汉诺威大鼠用高热量饮食处理10周。褪黑激素（5 mg/kg/d，p.o.，管饲法）给药2周。功能研究结果表明，肥胖引起的损失的抗收缩作用的PVAT和治疗与褪黑激素逆转这种反应。Tiron [一种超氧阴离子（O-2（-））清除剂]恢复了PVAT对肥胖大鼠膈肌的抗收缩作用，提示活性氧（ROS）在这种反应中起作用。肥胖大鼠主动脉周围PVAT中超氧化物歧化酶（SOD）活性降低，ROS水平升高。这些反应伴随着PVAT中一氧化氮（NO）水平的降低。褪黑激素治疗恢复SOD活性，降低ROS水平，增加NO生物利用度从肥胖大鼠PVAT。在这里，我们首次报道了褪黑激素对肥胖患者主动脉周围PVAT的有益作用。褪黑激素逆转肥胖对PVAT的不良影响，包括ROS的过度产生，降低SOD活性，降低NO的生物利用度。因此，PVAT可能是治疗肥胖引起的血管功能障碍的重要靶点，褪黑激素可能成为治疗肥胖引起的血管并发症的潜在工具。
Perivascular adipose tissue (PVAT) undergoes functional changes in obesity. Increased oxidative stress is a central mechanism whereby obesity induces loss of the anticontractile effect of PVAT. Melatonin is an antioxidant that displays vasoprotective action in cardiovascular disease. Here, we sought to investigate whether melatonin would restore the anticontractile effect of periaortic PVAT in obesity. Male Wistar Hannover rats were treated for 10 weeks with a high-calorie diet. Melatonin (5 mg/kg/d, p.o., gavage) was administered for 2 weeks. Functional findings showed that obesity-induced loss of the anticontractile effect of PVAT and treatment with melatonin reversed this response. Tiron [a scavenger of superoxide anion (O-2(-))] restored the anticontractile effect of PVAT in aortas from obese rats, suggesting a role for reactive oxygen species (ROS) in such response. Decreased superoxide dismutase (SOD) activity and augmented levels of ROS were detected in periaortic PVAT from obese rats. These responses were accompanied by decreased levels of nitric oxide (NO) in PVAT. Treatment with melatonin restored SOD activity, decreased ROS levels, and increased NO bioavailability in PVAT from obese rats. Here, we first reported the beneficial effects of melatonin in periaortic PVAT in obesity. Melatonin reversed the adverse effects of obesity in PVAT that included overproduction of ROS, reduced SOD activity, and decreased bioavailability of NO. Therefore, PVAT may constitute an important target for the treatment of obesity-induced vascular dysfunction and melatonin emerges as a potential tool in the management of the vascular complications induced by obesity.