Potentiation of Hypoxic Pulmonary Vasoconstriction by Hydrogen Sulfide Precursors 3-Mercaptopyruvate and D-Cysteine Is Blocked by the Cystathionine γ Lyase Inhibitor Propargylglycine
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 F2α 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 PGF2α 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.
KeywordsHypoxic pulmonary vasoconstriction 3-mercaptopyruvate D-cysteine
This study was supported by a Wellcome Trust Programme grant (087776) to PIA and Jeremy Ward.
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