Potentiation of Hypoxic Pulmonary Vasoconstriction by Hydrogen Sulfide Precursors 3-Mercaptopyruvate and D-Cysteine Is Blocked by the Cystathionine γ Lyase Inhibitor Propargylglycine

  • Jesus Prieto-Lloret
  • Philip I. AaronsonEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 860)


Although the gasotransmitter hydrogen sulfide (H2S) generally dilates systemic arteries in mammals, it causes constriction of pulmonary arteries. In isolated rat pulmonary arteries, we have shown that the H2S precursor cysteine enhances both hypoxic pulmonary vasoconstriction and tension development caused by the agonist prostaglandin F under normoxic conditions. These effects were blocked by propargylglycine (PAG), a blocker of the enzyme cystathionine γ lyase which metabolises cysteine to sulfide. In the present study, we evaluated whether 3-mercaptopyruvate (3-MP), a sulfide precursor which is thought to give rise to sulfide when it is metabolised by the enzyme mercaptopyruvate sulfurtransferase, also enhanced contraction. Application of 3-MP prior to hypoxic challenge caused a marked enhancement of HPV which was completely blocked by both L- and D,L-PAG (both 1 mM). Cumulative application of 3–1,000 μM 3-MP during an ongoing contraction to PGF under normoxic conditions also caused a marked increase in tension. Application of D-cysteine (1 mM) also enhanced HPV, and this effect was prevented by both the D-amino acid oxidase inhibitor sodium benzoate (500 μM) and 1 mM L-PAG.


Hypoxic pulmonary vasoconstriction 3-mercaptopyruvate D-cysteine 



This study was supported by a Wellcome Trust Programme grant (087776) to PIA and Jeremy Ward.


  1. Connolly MJ, Prieto-Lloret J, Becker S, Ward JP, Aaronson PI (2013) Hypoxic pulmonary vasoconstriction in the absence of pretone: essential role for intracellular Ca2+ release. J Physiol 591:4473–4498PubMedCrossRefPubMedCentralGoogle Scholar
  2. Kimura H (2014) The physiological role of hydrogen sulfide and beyond. Nitric Oxide 41C:4–10CrossRefGoogle Scholar
  3. Liu YH, Lu M, Hu LF, Wong PT, Webb GD, Bian JS (2012) Hydrogen sulfide in the mammalian cardiovascular system. Antioxid Redox Signal 17:141–185PubMedCrossRefGoogle Scholar
  4. Olson KR, Whitfield NL (2010) Hydrogen sulfide and oxygen sensing in the cardiovascular system. Antioxid Redox Signal 12:1219–1234PubMedCrossRefGoogle Scholar
  5. Olson KR, Dombkowski RA, Russell MJ, Doellman MM, Head SK, Whitfield NL et al (2006) Hydrogen sulfide as an oxygen sensor/transducer in vertebrate hypoxic vasoconstriction and hypoxic vasodilation. J Exp Biol 209:4011–4023PubMedCrossRefGoogle Scholar
  6. Olson KR, Whitfield NL, Bearden SE, St Leger LJ, Nilson E, Gao Y, Madden JA (2010) Hypoxic pulmonary vasodilation: a paradigm shift with a hydrogen sulfide mechanism. Am J Physiol Regul Integr Comp Physiol 298:R51–R60PubMedCrossRefPubMedCentralGoogle Scholar
  7. Olson KR, Deleon ER, Gao Y, Hurley K, Sadauskas V, Batz C et al (2013) Thiosulfate: a readily accessible source of hydrogen sulfide in oxygen sensing. Am J Physiol egul Integr Comp Physiol 305:R592–R603Google Scholar
  8. Prieto-Lloret J, Shaifta Y, Ward JPT, Aaronson PI (2014) Hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries is not inhibited by antagonists of H2S-synthesizing pathways. J Physiol 593:385–401Google Scholar
  9. Shibuya N, Kioke S, Tanaka M, Ishigami-Yuasa M, Kimura Y, Ogasawara K et al (2013) A novel pathway for the production of hydrogen sulfide from D-cysteine in mammalian cells. Nat Commun 4:1366–1372PubMedCrossRefGoogle Scholar
  10. Singh S, Banerjee R (2011) PLP-dependent H(2)S biogenesis. Biochim Biophys Acta 1814:1518–1527PubMedCrossRefPubMedCentralGoogle Scholar
  11. Wang R (2012) Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiol Rev 92:791–896PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Division of Asthma, Allergy & Lung Biology, Faculty of Life Sciences and MedicineKing’s College LondonLondonUK

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