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27 February 2018 : Animal Research  

Hydrogen Sulfide Attenuates Hypertensive Inflammation via Regulating Connexin Expression in Spontaneously Hypertensive Rats

Xin Ni12BC, Liang Zhang13CEG, Min Peng13BCF, Tu-Wang Shen13BF, Xiu-Shi Yu13F, Li-Ya Shan13F, Li Li13G, Jun-Qiang Si13G, Xin-Zhi Li14ADG, Ke-Tao Ma13ADG*

DOI: 10.12659/MSM.908761

Med Sci Monit 2018; 24: ANS1205-1218

Abstract

BACKGROUND: Hydrogen sulfide (H2S) has anti-inflammatory and anti-hypertensive effects, and connexins (Cxs) are involved in regulation of immune homeostasis. In this study, we explored whether exogenous H2S prevents hypertensive inflammation by regulating Cxs expression of T lymphocytes in spontaneously hypertensive rats (SHR).

MATERIAL AND METHODS: We treated SHR with sodium hydrosulfide (NaHS) for 9 weeks. Vehicle-treated Wistar-Kyoto rats (WKYs) were used as a control. The arterial pressure was monitored by the tail-cuff method, and vascular function in basilar arteries was examined by pressure myography. Hematoxylin and eosin staining was used to show vascular remodeling and renal injury. The percentage of T cell subtypes in peripheral blood, surface expressions of Cx40/Cx43 on T cell subtypes, and serum cytokines level were determined by flow cytometry or ELISA. Expression of Cx40/Cx43 proteins in peripheral blood lymphocytes was analyzed by Western blot.

RESULTS: Chronic NaHS treatment significantly attenuated blood pressure elevation, and inhibited inflammation of target organs, vascular remodeling, and renal injury in SHR. Exogenous NaHS also improved vascular function by attenuating KCl-stimulated vasoconstrictor response in basilar arteries of SHR. In addition, chronic NaHS administration significantly suppressed inflammation of peripheral blood in SHR, as evidenced by the decreased serum levels of IL-2, IL-6, and CD4/CD8 ratio and the increased IL-10 level and percentage of regulatory T cells. NaHS treatment decreased hypertension-induced Cx40/Cx43 expressions in T lymphocytes from SHR.

CONCLUSIONS: Our data demonstrate that H2S reduces hypertensive inflammation, at least partly due to regulation of T cell subsets balance by Cx40/Cx43 expressions inhibition.

Keywords: Connexins, Hydrogen Sulfide, Hypertension, Rats, Inbred SHR, T-Lymphocytes

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750