Hydrogen sulphide vasodilates human pulmonary arteries: A possible role in pulmonary hypertension?

Ariyaratnam, Priyadharshanan; Loubani, Mahmoud; Morice, Alyn H.

doi:10.1016/j.mvr.2013.09.002

Cited by 53 publications

(32 citation statements)

References 17 publications

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“…Incidentally, the ratio between systolic RV pressure and pulmonary blood flow, a marker of right ventricular afterload, was not different between the two groups. This is consistent with the study using human pulmonary artery which could only be dilated with a concentration 200 times higher than the concentrations we used in-vivo (500 microM of H 2 S [25]). Sun et al [26] also found differences in the response to NaHS between rat aortic and pulmonary arterial rings, the latter being less responsive to NaHS than aorta.…”

Section: Discussionsupporting

confidence: 91%

Sulfide Intoxication-Induced Circulatory Failure is Mediated by a Depression in Cardiac Contractility

Sonobe

Haouzi

2015

Cardiovasc Toxicol

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Hydrogen sulfide (H2S) intoxication produces a rapid cardio-circulatory failure leading to cardiac arrest. In non-lethal forms of sulfide exposure, the presence of a circulatory shock is associated with long-term neurological sequelae. Our aim was to clarify the mechanisms of H2S-induced circulatory failure. In anesthetized paralyzed and mechanically ventilated rats, cardiac output, arterial pressure and ventricular pressures were determined while NaHS was infused to increase arterial concentration of soluble H2S (CgH2S) from undetectable to levels leading to circulatory failure. Compared to control/saline infusion, blood pressure started to decrease significantly along with a modest drop in peripheral vascular resistance (-19 ± 5%, P<0.01), when CgH2S reached about 1 microM. As CgH2S exceeded 2-3 microM, parameters of ventricular contractility diminished with no further reduction in peripheral resistance. Whenever H2S exposure was maintained at a higher level (CgH2S over 7 microM), a clear inhibition of cardiac contractility was observed, leading to asystole within minutes, but with no evidence of peripheral vasoplegia. The immediate and long-term neurological effects of specifically counteracting sulfide induced cardiac contractility depression following H2S exposure remain to be investigated.

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Section: Discussionsupporting

confidence: 91%

Sulfide Intoxication-Induced Circulatory Failure is Mediated by a Depression in Cardiac Contractility

Sonobe

Haouzi

2015

Cardiovasc Toxicol

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“…4), demonstrating that neither the excess sulfide nor the oxidation products can account for the pronounced relaxation induced by the products of the Sulfide/GSNO interaction. Our findings are in agreement with other reports showing that low μM concentrations of sulfide neither relax pre-constricted mouse aortic strips [36] nor human lobar pulmonary arteries [37].…”

Section: Effects Of Sulfide Gsno Sn and The 'Ssno -Mix' On Aortic Csupporting

confidence: 94%

The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

et al. 2015

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A B S T R A C TThe chemical interaction of sodium sulfide (Na2S) with the NO-donor S-nitrosoglutathione (GSNO) has been described to generate new reaction products, including polysulfides and nitrosopersulfide (SSNO -) via intermediacy of thionitrous acid (HSNO). The aim of the present work was to investigate the vascular effects of the longer-lived products of the Sulfide/GSNO interaction. Here we show that the products of this reaction relax precontracted isolated rings of rat thoracic aorta and mesenteric artery (but to a lesser degree rat uterus) with a >2-fold potency compared with the starting material, GSNO (50 nM), whereas Na2S and polysulfides have little effect at 1-5 μM. The onset of vasorelaxation of the reaction products was 7-10 times faster in aorta and mesenteric arteries compared with GSNO. Relaxation to GSNO (100-500 nM) was blocked by an inhibitor of soluble guanylyl cyclase, ODQ (0.1 and 10 μM), and by the NO scavenger cPTIO (100 μM), but less affected by prior acidification (pH 2-4), and unaffected by N-acetylcysteine (1 mM) or methemoglobin (20 μM heme). By contrast, relaxation to the Sulfide/GSNO reaction products (100-500 nM based on the starting material) was inhibited to a lesser extent by ODQ, only slightly decreased by cPTIO, more markedly inhibited by methemoglobin and N-acetylcysteine, and abolished by acidification before addition to the organ bath. The reaction mixture was found to generate NO as detected by EPR spectroscopy using N-(dithiocarboxy)-N-methyl-D-glucamine (MGD2)-Fe 2+ as spin trap. In conclusion, the Sufide/GSNO reaction products are faster and more pronounced vasorelaxants than GSNO itself. We conclude that in addition to NO formation from SSNO -, reaction products other than polysulfides may give rise to nitroxyl (HNO) and be involved in the pronounced relaxation induced by the Sulfide/GSNO cross-talk.

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“…Al-Magableh and Hart (2011) and Hedegaard et al 2014)). As a result of these studies, H 2 S is often described as a "potent vasodilator" (Bhatia 2005;Pushpakumar et al 2014;Ariyaratnam et al 2013;Jang et al 2014;Baragatti et al 2013;Ghasemi et al 2012) despite data clearly showing otherwise. However, the addition of GYY4137 at concentrations and incubation times which deliver nM to low μM H 2 S also leads to vasodilation in vitro and in vivo (Table 1) suggesting blood vessels are acutely sensitive to small fluxes of H 2 S when it is generated in a manner and a level comparable to enzymatic (e.g.…”

Section: Gyy4137: Vascular Effectsmentioning

confidence: 99%

Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors

Whiteman

Perry

Zhou³

et al. 2015

Handbook of Experimental Pharmacology

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Hydrogen sulfide is rapidly emerging as a key physiological mediator and potential therapeutic tool in numerous areas such as acute and chronic inflammation, neurodegenerative and cardiovascular disease, diabetes, obesity and cancer. However, the vast majority of the published studies have employed crude sulfide salts such as sodium hydrosulfide (NaSH) and sodium sulfide (Na2S) as H2S "donors" to generate H2S. Although these salts are cheap, readily available and easy to use, H2S generated from them occurs as an instantaneous and pH-dependent dissociation, whereas endogenous H2S synthesis from the enzymes cystathionine γ-lyase, cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase is a slow and sustained process. Furthermore, sulfide salts are frequently used at concentrations (e.g. 100 μM to 10 mM) far in excess of the levels of H2S reported in vivo (nM to low μM). For the therapeutic potential of H2S is to be properly harnessed, pharmacological agents which generate H2S in a physiological manner and deliver physiologically relevant concentrations are needed. The phosphorodithioate GYY4137 has been proposed as "slow-release" H2S donors and has shown promising efficacy in cellular and animal model diseases such as hypertension, sepsis, atherosclerosis, neonatal lung injury and cancer. However, H2S generation from GYY4137 is inefficient necessitating its use at high concentrations/doses. However, structural modification of the phosphorodithioate core has led to compounds (e.g. AP67 and AP105) with accelerated rates of H2S generation and enhanced biological activity. In this review, the therapeutic potential and limitations of GYY4137 and related phosphorodithioate derivatives are discussed.

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Hydrogen sulphide vasodilates human pulmonary arteries: A possible role in pulmonary hypertension?

Cited by 53 publications

References 17 publications

Sulfide Intoxication-Induced Circulatory Failure is Mediated by a Depression in Cardiac Contractility

Sulfide Intoxication-Induced Circulatory Failure is Mediated by a Depression in Cardiac Contractility

The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors

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