Adrenomedullin Improves Hypertension and Vascular Remodeling partly through the Receptor-Mediated AMPK Pathway in Rats with Obesity-Related Hypertension.
Adrenomedullin Improves Hypertension and Vascular Remodeling partly through the Receptor-Mediated AMPK Pathway in Rats with Obesity-Related Hypertension.
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DOI：
10.3390/ijms24043943
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发表时间：
2023-02-15
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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肾上腺髓质素（ADM）是一种具有抗炎和抗氧化作用的新型心血管肽。慢性炎症、氧化应激和钙化在肥胖相关性高血压（obesity-related hypertension， OH）血管功能障碍的发病机制中起关键作用。本研究旨在探讨ADM对OH大鼠血管炎症、氧化应激和钙化的影响。8周龄的雄性大鼠分别饲喂对照饮食和高脂饮食（HFD） 28周。然后将OH大鼠随机分为两组：(1)HFD对照组，(2)HFD合并ADM组。ADM （7.2 μg/kg/d, ip）治疗4周，不仅能改善OH大鼠高血压和血管重构，还能抑制血管炎症、氧化应激和主动脉钙化。在体外实验中，ADM （10 nM）对A7r5细胞（大鼠胸主动脉平滑肌细胞）单用或联合使用棕榈酸（PA, 200 μM）或血管紧张素II （Ang II, 10 nM）治疗诱导的炎症、氧化应激和钙化均有减弱作用，而ADM受体拮抗剂ADM22-52和amp活化蛋白激酶（AMPK）抑制剂Compound C分别有效抑制了这两种作用。此外，ADM处理显著抑制OH大鼠主动脉或pa处理的A7r5细胞中Ang II型1受体（AT1R）蛋白的表达。ADM通过受体介导的AMPK途径部分改善高血压、血管重构和动脉硬化，减轻OH状态下的炎症、氧化应激和钙化。该结果也提出了ADM将被考虑用于改善OH患者高血压和血管损伤的可能性。
Adrenomedullin (ADM) is a novel cardiovascular peptide with anti-inflammatory and antioxidant properties. Chronic inflammation, oxidative stress and calcification play pivotal roles in the pathogenesis of vascular dysfunction in obesity-related hypertension (OH). Our study aimed to explore the effects of ADM on the vascular inflammation, oxidative stress and calcification in rats with OH. Eight-week-old Sprague Dawley male rats were fed with either a Control diet or a high fat diet (HFD) for 28 weeks. Next, the OH rats were randomly subdivided into two groups as follows: (1) HFD control group, and (2) HFD with ADM. A 4-week treatment with ADM (7.2 μg/kg/day, ip) not only improved hypertension and vascular remodeling, but also inhibited vascular inflammation, oxidative stress and calcification in aorta of rats with OH. In vitro experiments, ADM (10 nM) in A7r5 cells (rat thoracic aorta smooth muscle cells) attenuated palmitic acid (PA, 200 μM) or angiotensin II (Ang II, 10 nM) alone or their combination treatment-induced inflammation, oxidative stress and calcification, which were effectively inhibited by the ADM receptor antagonist ADM22-52 and AMP-activated protein kinase (AMPK) inhibitor Compound C, respectively. Moreover, ADM treatment significantly inhibited Ang II type 1 receptor (AT1R) protein expression in aorta of rats with OH or in PA-treated A7r5 cells. ADM improved hypertension, vascular remodeling and arterial stiffness, and attenuated inflammation, oxidative stress and calcification in OH state partially via receptor-mediated AMPK pathway. The results also raise the possibility that ADM will be considered for improving hypertension and vascular damage in patients with OH.
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影响因子：
12.8
作者：
Jeon SM
通讯作者：
Jeon SM
影响因子：
3.8
作者：
Dai, Hang-Bing;Wang, Hong-Yu;Zhou, Ye-Bo
通讯作者：
Zhou, Ye-Bo
影响因子：
--
作者：
Nomura, Ikuo;Kato, Johji;Kitamura, Kazuo
通讯作者：
Kitamura, Kazuo
影响因子：
3.6
作者：
Donis N;Jiang Z;D'Emal C;Hulin A;Debuisson M;Dulgheru R;Nguyen ML;Postolache A;Lallemand F;Coucke P;Martinive P;Herzog M;Pamart D;Terrell J;Pincemail J;Drion P;Delvenne P;Nchimi A;Lancellotti P;Oury C
通讯作者：
Oury C
DOI：
10.1161/atvbaha.118.311229
发表时间：
2018-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Brown IAM;Diederich L;Good ME;DeLalio LJ;Murphy SA;Cortese-Krott MM;Hall JL;Le TH;Isakson BE
通讯作者：
Isakson BE