Shuo Sun1,2, Feng Zhang1,2, Yan Pan1,2, Yu Xu1,2, Aidong Chen1,2, Jian Wang3, Haiyang Tang4,5, Ying Han6,7. 1. Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. 2. Department of Physiology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. 3. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China. 4. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China. tanghy2008@yahoo.com. 5. College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China. tanghy2008@yahoo.com. 6. Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. yhancn@njmu.edu.cn. 7. Department of Physiology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. yhancn@njmu.edu.cn.
Abstract
PURPOSE: Attenuated vasodilatation of small arteries is a hallmark feature of hypertension. Salusin-β, 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-β 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-β 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-β increased arterial blood pressure in SHR, while anti-salusin-β IgG decreased it. Salusin-β further deteriorated, while anti-salusin-β 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-β 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-β but reduced by anti-salusin-β IgG. ROS scavenger NAC or antioxidant apocynin significantly inhibited, while SOD inhibitor DETC aggravated, the effects of salusin-β, and the eNOS inhibitor L-NAME inhibited the effects of anti-salusin-β IgG. CONCLUSIONS: These results indicated that enhanced salusin-β 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.
PURPOSE: Attenuated vasodilatation of small arteries is a hallmark feature of hypertension. Salusin-β, 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-β 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-β 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-β increased arterial blood pressure in SHR, while anti-salusin-β IgG decreased it. Salusin-β further deteriorated, while anti-salusin-β 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-β 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-β but reduced by anti-salusin-β IgG. ROS scavenger NAC or antioxidant apocynin significantly inhibited, while SOD inhibitor DETC aggravated, the effects of salusin-β, and the eNOS inhibitor L-NAME inhibited the effects of anti-salusin-β IgG. CONCLUSIONS: These results indicated that enhanced salusin-β 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.
Authors: Aram V Chobanian; George L Bakris; Henry R Black; William C Cushman; Lee A Green; Joseph L Izzo; Daniel W Jones; Barry J Materson; Suzanne Oparil; Jackson T Wright; Edward J Roccella Journal: Hypertension Date: 2003-12-01 Impact factor: 10.190
Authors: Xuanxuan Liu; Xingxing Wang; Yan Pan; Li Zhao; Shuo Sun; Ang Luo; Changlei Bao; Haiyang Tang; Ying Han Journal: Drug Des Devel Ther Date: 2021-11-02 Impact factor: 4.162