Cardioprotection of H2S by downregulating iNOS and upregulating HO-1 expression in mice with CVB3-induced myocarditis.

Aims: To explore the effects and potential mechanisms of hydrogen sulfide (H2S) in CVB3-induced mice with myocarditis.

Main Methods: A total of 75 six-week-old inbred male Balb/c mice were divided randomly into four groups (N, C, P and S). Group N was the negative control. The others were inoculated intraperitoneally (i.p.) with CVB3. Subsequently, groups P and S were injected i.p. once a day with DL-Proparglygylcine (PAG) and NaHS respectively. Group C was the positive control. Inducible nitric oxide synthase (iNOS) and heme oxygenase-1(HO-1) expression on cardiac tissues were evaluated by histopathological examination, immunohistochemistry, RT-PCR and Western blot.

Key Findings: The heart-weight to body-weight (HW/BW) ratio, the histologic scores and the iNOS mRNA and protein expression levels were higher, and the HO-1 mRNA and protein expression levels were lower in mice treated with PAG than those mice solely inoculated with CVB3. Mice in group S had a significant decreased in the HW/BW ratio, the histologic scores and the iNOS mRNA and protein expression levels, and had a significant increased in the HO-1 mRNA and protein expression levels compared to the mice in group C. H2S can attenuate inflammatory cell infiltration, alleviate cardiac edema, and limit myocardial lesions.

Significance: Our data support that H2S can inhibit iNOS overexpression and induce HO-1 expression, both of which contribute to the cardioprotection of H2S in CVB3-induced mice myocarditis.