AIMS: Cardiac local renin-angiotensin system plays an important role in the development of heart failure and left ventricular (LV) remodeling. We previously reported that hydrogen sulfide (H2S), an endogenous gaseous mediator, regulates renin synthesis and release in juxtaglomerular cells. The present study was designed to investigate whether H2S can protect against isoproterenol (ISO)-induced heart failure via inhibition of local renin activity in rat hearts. RESULTS: In the present study, we found that an injection of ISO (150 mg/kg) significantly increased plasma lactate dehydrogenase level and hypertrophy index and impaired LV end diastolic pressure. Treatment with NaHS (an H2S donor, 0.056 mg/kg, daily) 3 days before and 2 weeks after the ISO injection attenuated the development of heart failure. Histological staining showed that NaHS decreased ISO-induced collagen deposition. Moreover, NaHS treatment reversed ISO-induced renin elevation in both plasma and LVs. Immunostaining analysis indicated that renin expression co-localized with mast cells in the ventricular tissues. Mast cell counts showed that NaHS treatment decreased the number of degranulated mast cells in cardiac tissue due to down-regulation of leukotriene A4 hydrolase protein expression and leukotriene B4 level. In addition, NaHS treatment also inhibited forskolin-induced renin degranulation from HMC-1.1 mast cells by lowering intracellular cAMP level. INNOVATION: This study provides evidence for a new pathway in H2S-induced cardioprotection against heart failure development. CONCLUSIONS: For the first time, we demonstrated that H2S might protect heart during heart failure by suppression of local renin level through inhibition of both mast cell infiltration and renin degranulation.
AIMS: Cardiac local renin-angiotensin system plays an important role in the development of heart failure and left ventricular (LV) remodeling. We previously reported that hydrogen sulfide (H2S), an endogenous gaseous mediator, regulates renin synthesis and release in juxtaglomerular cells. The present study was designed to investigate whether H2S can protect against isoproterenol (ISO)-induced heart failure via inhibition of local renin activity in rat hearts. RESULTS: In the present study, we found that an injection of ISO (150 mg/kg) significantly increased plasma lactate dehydrogenase level and hypertrophy index and impaired LV end diastolic pressure. Treatment with NaHS (an H2Sdonor, 0.056 mg/kg, daily) 3 days before and 2 weeks after the ISO injection attenuated the development of heart failure. Histological staining showed that NaHS decreased ISO-induced collagen deposition. Moreover, NaHS treatment reversed ISO-induced renin elevation in both plasma and LVs. Immunostaining analysis indicated that renin expression co-localized with mast cells in the ventricular tissues. Mast cell counts showed that NaHS treatment decreased the number of degranulated mast cells in cardiac tissue due to down-regulation of leukotriene A4 hydrolase protein expression and leukotriene B4 level. In addition, NaHS treatment also inhibited forskolin-induced renin degranulation from HMC-1.1 mast cells by lowering intracellular cAMP level. INNOVATION: This study provides evidence for a new pathway in H2S-induced cardioprotection against heart failure development. CONCLUSIONS: For the first time, we demonstrated that H2S might protect heart during heart failure by suppression of local renin level through inhibition of both mast cell infiltration and renin degranulation.