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

Abstract

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.

β‑estradiol alleviates hypertension‑ and concanavalin A‑mediated inflammatory responses via modulation of connexins in peripheral blood lymphocytes

“…Tail systolic arterial pressure was recorded in conscious and calm rats at 21 weeks old using a non-invasive tail-cuff apparatus (Chengdu Taimeng Software Co. Ltd., Chengdu, China) without heating, as described in the authors' previous study (13,27). The BP of each rat was taken as the average of at least three stable consecutive measurements following removal of outliers and any readings associated with excess noise or animal movement on each occasion.…”

“…Fixed renal and vascular tissues from the different groups were dehydrated in graded concentrations of ethanol and imbedded in paraffin, then 5 µm-thick sections were cut with a microtome. Kidney and BA sections were stained with hematoxylin and eosin as described in the authors' previous study (13). Histological observation of vascular remodeling and renal injury was performed using light microscopy (Olympus BX50 microscope; Olympus Corporation, Tokyo, Japan).…”

“…Expression of Cx40 and Cx43 on CD4 + or CD8 + T cells was determined by flow cytometry as previously described, with minor modifications (11,13). Briefly, permeabilized PBMCs were incubated with anti-Cx40 monoclonal antibody (dilution 1:500; cat.…”

“…Although the role of T lymphocytes in hypertension-mediated inflammation is clearly defined by a large body of experimental data, the evidence that inflammation and an adaptive immune response are induced by hypertension is rather limited. The authors' laboratory has demonstrated that gap junctional communication via connexins (Cxs) in peripheral blood lymphocytes of SHRs (10) and hypertensive patients (11) is involved in the hypertension-mediated inflammatory response, and that Cx expression is positively correlated with the proliferation of T lymphocyte and production of pro-inflammatory cytokines in the peripheral blood of patients with hypertension and SHRs (10–13). Data from the authors' laboratory and other groups have also revealed that inhibition of Cx43-mediated gap junctional communication can reduce the activation and proliferation of T lymphocytes and production of pro-inflammatory cytokines under various pro-inflammatory stimuli (10,11,14–16).…”

Gas‐Generating Nanoplatforms: Material Chemistry, Multifunctionality, and Gas Therapy

“…In addition to the mostly explored oxygen (O 2 ), nitric oxide (NO), and carbon monoxide (CO) as the therapeutic gases, hydrogen sulfide (H 2 S) has also been demonstrated to be the common gaseous transmitter providing diverse physiological and pathophysiological effects in the body, which is endogenously produced from cysteine as activated by certain enzymes such as cystathionine β‐synthase, cystathionine γ‐lyase, and 3‐mercaptopyruvate sulfur transferase . Therefore, H 2 S has been revealed to be related to versatile physiological processes such as anti‐inflammation, antioxidant defense response, neuromodulation, metabolic suppression, etc.…”