A TOR2A Gene Product: Salusin-β Contributes to Attenuated Vasodilatation of Spontaneously Hypertensive Rats
A TOR2A Gene Product: Salusin-β Contributes to Attenuated Vasodilatation of Spontaneously Hypertensive Rats
复制标题
TOR2A 基因产物：Salusin-beta 有助于减弱自发性高血压大鼠的血管舒张作用
DOI：
10.1007/s10557-020-06983-1
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发表时间：
2020-05-26
影响因子：
3.4
通讯作者：
Han, Ying
中科院分区：
文献类型：
--
作者：
Sun, Shuo;Zhang, Feng;Han, Ying
目的小动脉舒张功能减弱是高血压的一个标志性特征。Salusin-beta是TOR 2A基因的产物，是一种重要的血管活性肽，与心血管疾病关系密切。本研究旨在探讨salusin-beta在Wistar-Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）血管舒张中的作用及其信号通路。结果SHR血浆salusin-β水平及其在冠状动脉（CA）、肠系膜动脉（MA）和肺动脉（PA）的蛋白表达均显著高于WKY。salusin-β使SHR动脉血压升高，抗salusin-β IgG使血压降低，salusin-β使血压进一步恶化，抗salusin-β IgG使血压改善，降低ACh舒张作用，降低SHR动脉一氧化氮（NO）水平和内皮型一氧化氮合酶（eNOS）活性，salusin-β对SNP舒张作用无明显影响。SHR动脉组织中NAD（P）H氧化酶活性和活性氧（ROS）水平明显高于WKY，salusin-β可进一步升高SHR动脉组织中的NAD（P）H氧化酶活性和ROS水平，而salusin-β IgG可降低SHR动脉组织中的NAD（P）H氧化酶活性和ROS水平。ROS清除剂NAC或抗氧化剂夹竹桃素（apocynin）可显著抑制上述作用，SOD抑制剂DETC则可加重上述作用，salusin-β可增强上述作用，而eNOS抑制剂L-NAME则可抑制抗salusin-β IgG的作用。结论salusin-β活性增强可能通过激活NAD（P）H氧化酶产生的ROS，抑制eNOS激活和NO释放，从而减轻SHR血管内皮依赖性舒张的发病机制。
Purpose Attenuated vasodilatation of small arteries is a hallmark feature of hypertension. Salusin-beta, which is a TOR2A gene product and an important vasoactive peptide, has a close relationship with cardiovascular disease. This study aimed to determinate the roles of salusin-beta in vasodilatation, and its signal pathways in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR).Methods Isometric tension experiments were performed. Vasodilatation was induced by acetylcholine (ACh) or sodium nitroprusside (SNP).Results Plasma salusin-beta levels and their protein expressions in coronary artery (CA), mesenteric artery (MA), and pulmonary artery (PA) of SHR were much higher than that of WKY. Intravenous injection of salusin-beta increased arterial blood pressure in SHR, while anti-salusin-beta IgG decreased it. Salusin-beta further deteriorated, while anti-salusin-beta IgG improved, the attenuated ACh-induced relaxation, the decreased nitric oxide (NO) level, and endothelial nitric oxide synthase (eNOS) activity in arteries of SHR, and salusin-beta had no significant effect on SNP-induced relaxation. The NAD(P)H oxidase activity and reactive oxygen species (ROS) level in arteries of SHR were much higher than that of WKY, which was further increased by salusin-beta but reduced by anti-salusin-beta IgG. ROS scavenger NAC or antioxidant apocynin significantly inhibited, while SOD inhibitor DETC aggravated, the effects of salusin-beta, and the eNOS inhibitor L-NAME inhibited the effects of anti-salusin-beta IgG.Conclusions These results indicated that enhanced salusin-beta activity is involved in attenuated endothelium-dependent vasodilatation pathogenesis in SHR by activating NAD(P)H oxidase derived ROS generation and inhibiting eNOS activation and NO release.