Hydrogen Sulfide Attenuates Renin Angiotensin and Aldosterone Pathological Signaling to Preserve Kidney Function and Improve Exercise Tolerance in Heart Failure

Abstract

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Hydrogen Sulfide Therapy Promotes Beneficial Systemic Effects in Experimental Heart Failure

“…It is feasible that the effects of JK-1 observed by Li et al. (3) may involve local actions in the heart, vasculature, and kidneys. However, the study design does not exclude the possibility that some of the salubrious extracardiac effects might be secondary to improved cardiac function or related to reduction in SNS/RAAS activation.…”

“…Its tolerability, dosing, safety, and efficacy have previously been established by this group in a mouse model of ischemia-reperfusion myocardial injury in which intramyocardial injections were used to deliver JK-1 (10). In the current study (3), the authors administered intraperitoneal injections of JK-1 commencing either 3 or 10 weeks after transverse aortic constriction (TAC). Although the early treatment had a greater magnitude of effect on LV ejection fraction and remodeling, treatment at 10 weeks also led to a significant delay of adverse heart failure phenotypes at 18 weeks compared with the untreated group.…”

“…In this issue of JACC: Basic to Translational Science, Li et al. (3) investigated the effects of a novel class of therapeutic agents, namely hydrogen-sulfide (H 2 S)-based drugs. Although the efficacy of these agents has previously been studied immediately after pathological insults (e.g., experimental myocardial infarction and pressure overload) (4), here the focus was on a relatively delayed administration of an H 2 S-donor, JK-1, in an attempt to more closely parallel the clinical setting.…”

“…Li et al. (3) found that in a murine model of pressure overload-induced heart failure, the administration of JK-1 after the development of cardiac remodeling was able to significantly delay the progression of remodeling and contractile impairment. Moreover, they observed a significant improvement in renal dysfunction, endothelial dysfunction, and exercise tolerance compared with untreated animals, therefore achieving a combination of beneficial systemic effects.…”

“…Li et al. (3) are to be commended for designing a study that investigates delayed treatment in an experimental heart failure model. In particular, their global analysis approach with the inclusion of renal function and exercise duration readouts goes beyond the common cardiocentric view of experimental heart failure in rodent models.…”