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A TOR2A Gene Product: Salusin-β Contributes to Attenuated Vasodilatation of Spontaneously Hypertensive Rats

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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.

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Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was sponsored by the National Natural Science Foundation of China [31571168, 81470538, 81770059, and 81770050], Qing Lan Project of Jiangsu Province of China, and the Open Project of the State Key Laboratory of Respiratory Disease (SKLRD-OP-201911).

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Author notes

  1. Shuo Sun and Feng Zhang contributed equally to this work.

Authors and Affiliations

  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

    Shuo Sun, Feng Zhang, Yan Pan, Yu Xu, Aidong Chen & Ying Han

  2. Department of Physiology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China

    Shuo Sun, Feng Zhang, Yan Pan, Yu Xu, Aidong Chen & Ying Han

  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

    Jian Wang & Haiyang Tang

  4. College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China

    Haiyang Tang

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  1. Shuo Sun
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  2. Feng Zhang
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  3. Yan Pan
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  4. Yu Xu
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Contributions

All authors contributed to the work in this paper. Y.H. and H.T. conceived and designed the experiments. S.S., F.Z., Y.X., and Y.P. performed the experiments. S.S. and A.D.C analyzed the data. Y.H. and H.T. wrote the manuscript. J.W. and H.T. provided intellectual suggestions and critically revised the article.

Corresponding authors

Correspondence to Haiyang Tang or Ying Han.

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The authors declare that they have no conflict of interest.

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All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All animal procedures were reviewed and approved by Nanjing Medical University Experimental Animal Care and in accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication, 8th edition, 2011).

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Sun, S., Zhang, F., Pan, Y. et al. A TOR2A Gene Product: Salusin-β Contributes to Attenuated Vasodilatation of Spontaneously Hypertensive Rats. Cardiovasc Drugs Ther 35, 125–139 (2021). https://doi.org/10.1007/s10557-020-06983-1

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