BackgroundHydrogen 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/MethodsWe 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.ResultsChronic 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.ConclusionsOur data demonstrate that H2S reduces hypertensive inflammation, at least partly due to regulation of T cell subsets balance by Cx40/Cx43 expressions inhibition.

Background: Progressive fibrosis accompanies all chronic renal disease, connective tissue growth factor (CTGF,) and platelet-derived growth

Hypoxic exposure results in the vascular dysfunction and reduction of vasomotor responses and thus disrupts or reduces blood flow in the resistance arteries. Connexin (Cx)-mediated gap junctional intercellular communication (GJIC) serves a critical role in the regulation of vasomotor tone and the synchronized contraction of arteries, however whether the adverse effect of hypoxia on vasomotor responses in vascular smooth muscle layer of resistance arteries is involved in changes in the GJIC and the expression of Cx43 and Cx45 remains to be elucidated. Pressure myography, whole-cell patch clamp and western blot analysis were used to investigate the differences in expression and function of gap junction (GJ) in the vascular smooth muscle cells (VSMCs) of the mesenteric resistance artery (MRA) from Sprague‑Dawley (SD) rats in normoxia and acute hypoxia groups. In the present study, whole‑cell patch clamp measurements demonstrated a significant reduction in the membrane capacitance and conductance in the VSMCs of the MRAs in the acute hypoxia (5 min) group (n=13) compared with the normoxia group (n=13), which suggested that exposure to acute hypoxia of 5 min decreased the coupling of the GJ between the VSMCs of MRAs in SD rats. Pressure myographic analysis demonstrated that 0.1‑100 µM phenylephrine (PE)‑induced MRA vasoconstriction was less sensitive under the acute hypoxic condition (n=7) compared with the normoxia condition (n=9) following treatment with 100 µM 2‑aminoethoxydiphenyl borate for 20 min. Compared with SD rats under normoxia, the PE‑initiated vasoconstrictive frequency and amplitude under acute hypoxia for 20, 40 and 60 min in the MRAs of SD rats was markedly attenuated (n=7). The results of western blot analysis indicated that the expression levels of Cx43 and Cx45 in MRA under acute hypoxia (1 h) were lower compared with normoxia. Cx43‑and Cx45‑mediated GJs serve a significant role in the regulation of the vasomotor function of MRA during hypoxia and may be essential for the adjustment of vasomotor tone in response to acute hypoxia.