Hydrogen sulfide inhibits human platelet aggregation

Abstract

Gaseous mediators such as nitric oxide (NO) play a major regulatory role in the cardiovascular system homeostasis, including platelet aggregation. Here, we investigated whether hydrogen sulfide (H₂S), a newly recognized endogenous mediator, can affects aggregation of human platelets, using sodium hydrogen sulfide (NaHS) as H₂S-donor. NaHS inhibited platelet aggregation induced by ADP, collagen, epinephrine, arachidonic acid, thromboxane mimetic, U46619, and thrombin. H₂S effect was not dependent by cAMP/cGMP generation, NO production or potassium-channels opening. NaHS concentrations (up to 10 mM) did not exert toxic effects on platelet viability. The possible protective role of endogenous H₂S in cardiovascular system is discussed.

Introduction

Hydrogen sulfide (H₂S) is a malodorous gas that, following acute/massive inhalation, may produce toxic effects (Beauchamp et al., 1984). However, H₂S is also endogenously generated from the metabolism of both cysteine and homocysteine (Moore et al., 2003). Micromolar levels of H₂S have been detected in brain, blood and other peripheral organs, mostly produced through two enzymatic pathways: cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) (Hosoki et al., 1997, Eto and Kimura, 2002). It has been shown that exogenously administered H₂S relaxes isolated blood vessels and induces transient hypotension via activation of ATP-sensitive K⁺-channels (K_ATP) (Zhao et al., 2001). It has been speculated that endogenous H₂S, similarly to nitric oxide (NO), might contribute to the maintenance of the cardiovascular homeostasis. In fact, decreased of plasma level H₂S were found in systemic or pulmonary hypertensive rats (Chunyu et al., 2003, Yan et al., 2004), while normal blood pressure was restored by administration of NaHS, an H₂S generating salt (Yan et al., 2004). In contrast, massive hyperproduction of endogenous H₂S seems to be responsible for hypotension caused by experimental septic/endotoxic shock (Collin et al., 2005). The discovery that H₂S is endogenously generated within the heart, where it might play a cardioprotective function against ischemic injury (Pan et al., 2005, Bian et al., 2006), reinforces the hypothesis that H₂S might act as a protective agent in the cardiovascular system.

In the present study we have addressed the question whether H₂S can affect platelet aggregation. Our results indicate that H₂S inhibits aggregation of human platelets in vitro in a concentration-dependent manner, and suggest the possibility that changes of circulating H₂S might have a role in thromboembolic diseases.