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Adrenomedullin improved endothelial dysfunction via receptor-Akt pathway in rats with obesity-related hypertension

Hypertension Research (2024)Cite this article

Abstract

Obesity-related hypertension (OH) is accompanied by obvious endothelial dysfunction, which contributes to increased peripheral vascular resistance and hypertension. Adrenomedullin (ADM), a multifunctional active peptide, is elevated in obese humans. The OH rats induced by high fat diet (HFD) for 28 weeks and the human umbilical vein endothelial cells (HUVECs)-treated by palmitic acid (PA) were used to investigate the effects of ADM on endothelial dysfunction and the underlying mechanisms. Vascular reactivity was assessed using mesenteric arteriole rings, and the protein expression levels were examined by Western blot analysis. Compared with the control rats, OH rats exhibited hypertension and endothelial dysfunction, along with reduced eNOS protein expression and Akt activation, and increased protein expression of proinflammatory cytokines and ROS levels. Four-week ADM administration improved hypertension and endothelial function, increased eNOS protein expression and Akt activation, and attenuated endothelial inflammation and oxidative stress in OH rats. In vitro experiment, the antagonism of ADM receptors with ADM22-52 and the suppression of Akt signaling with A6730 significantly blocked ADM-caused increase of NO content and activation of eNOS and Akt, and inhibited the anti-inflammatory and anti-oxidant effect of ADM in PA-stimulated HUVECs. These data indicate that endothelial dysfunction in OH rats is partially attributable to the decreased NO level, and the increased inflammation and oxidative stress. ADM improves endothelial function and exerts hypotensive effect depending on the increase of NO, and its anti-inflammatory and anti-oxidant effect via receptor-Akt pathway.

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The data of this study will be available from the authors according to reasonable requests.

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Acknowledgements

All the authors thank the support of the Collaborative Innovation Center of Cardiovascular Disease Translational Medicine.

Funding

This work was funded by the National Nature Science Foundation of China (81970356), the Foundation from the Department of Health of Jiangsu Province, China (LKM2023029) and the Scientific Research Project of Jiangsu Health Commission (Z2018033).

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Author notes

  1. These authors contributed equally: Si-Yu Liu, Qian Wang, Hong Zhou, Ning Tong.

Authors and Affiliations

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

    Si-Yu Liu, Qian Wang, Hong Zhou, Rui Chang, Fang-Zheng Wang, Ye-Bo Zhou & Zhen-Zhen Li

  2. Department of Neurology of Heze Municipal Hospital, Heze, 274000, China

    Ning Tong

  3. Department of Cardiology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University Nanjing, Nanjing, 210021, Jiangsu, China

    Ping Guo, Xin Li & Zhen-Zhen Li

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Liu, SY., Wang, Q., Zhou, H. et al. Adrenomedullin improved endothelial dysfunction via receptor-Akt pathway in rats with obesity-related hypertension. Hypertens Res (2024). https://doi.org/10.1038/s41440-024-01701-y

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