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Reversal of deleterious effect of hypertension on the liver by inhibition of endoplasmic reticulum stress

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Abstract

Hypertension is an important risk factor for cardiovascular diseases. Besides cardiovascular system, it could cause damage to liver. It has been shown that endoplasmic reticulum stress (ERS) plays a crucial role in the pathogenesis of hypertension. ERS inhibitor tauroursodeoxycholic-acid (TUDCA) has favorable effects on various pathologies including cardiovascular, metabolic and hepatic diseases. In this study, the hepatoprotective effect and mechanism of TUDCA were investigated in the deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Male Wistar rats were used and divided into four groups: Control, DOCA, TUDCA and DOCA + TUDCA. Hypertension was induced by DOCA-salt administration for twelve weeks after the unilateral nephrectomy. TUDCA was given for the last 4 weeks. Systolic blood pressure was measured by using tail-cuff method. At the end of the treatment, liver was isolated and weighed. The expressions of various proteins and histopathological evaluation were examined in the liver. TUDCA markedly decreased systolic blood pressure in the hypertensive animals. Hypertension caused increase in the expressions of glucose-regulated protein-78 (GRP78), matrix metalloproteinase-2 (MMP-2) and phospho-inhibitor κB-α (p-IκB-α) and the decrease in the expression of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase2 (SERCA2) and phospho-extracellular signal-regulated kinase (p-ERK) in the liver. Alterations in these protein expressions were not detected in the TUDCA-treated hypertensive group. Also, hepatic balloon degeneration, inflammation and fibrosis were observed in the hypertensive group. TUDCA improved inflammation and fibrosis in the hypertensive liver. Our findings indicate that the detrimental effect of DOCA-salt-induced hypertension on the liver was defended by the inhibition of ERS. Hepatic ERS and its treatment should be taken into consideration for therapeutic approaches to hypertension.

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Acknowledgements

The authors are thankful to Prof. Dr. H. Gurdal and B. Dalkilic for supporting this research with the Western Blot experiments.

Funding

This research was funded by the Ankara University Research Foundation (Grant No. 16B0230004).

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, Gazi University, Etiler, 06330, Ankara, Turkey

    Nur Banu Bal, Sevtap Han & Mecit Orhan Uludag

  2. Department of Pathology, Faculty of Medicine, Ankara University, Sihhiye, 06100, Ankara, Turkey

    Saba Kiremitci

  3. Department of Medical Pharmacology, Faculty of Medicine, Ankara University, Sihhiye, 06100, Ankara, Turkey

    Emine Demirel-Yilmaz

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Bal, N.B., Han, S., Kiremitci, S. et al. Reversal of deleterious effect of hypertension on the liver by inhibition of endoplasmic reticulum stress. Mol Biol Rep 47, 2243–2252 (2020). https://doi.org/10.1007/s11033-020-05329-2

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