Hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries is not inhibited by antagonists of H2S-synthesizing pathways

TY - JOUR

T1 - Hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries is not inhibited by antagonists of H2S-synthesizing pathways

AU - Prieto-Lloret, Jesus

AU - Shaifta, Yasin

AU - Ward, Jeremy

AU - Aaronson, Philip

PY - 2015/1/15

Y1 - 2015/1/15

N2 - We evaluated the hypothesis that an increase in the hydrogen sulfide concentration in pulmonary artery smooth muscle cells causes hypoxic pulmonary vasoconstriction (HPV) by examining the effects of the sulfide donor cysteine and sulfide-synthesis blockers on HPV in isolated rat intrapulmonary arteries (IPA).Cysteine (1 mM) enhanced HPV and also the contraction to PGF2 and both effects were abolished by the cystathionine  lyase blocker propargylglycine (PAG, 1 mM), which had little or no non-selective effect on contraction at this concentration. Neither PAG nor the cysteine aminotransferase antagonist aspartate affected HPV in normal PSS, or in PSS containing physiological concentrations of cysteine, cystine and glutamate, whereas dithiothreitol (DTT), proposed to enhance HPV by converting mitochondrial thiosulfate to sulfide, instead abolished HPV. PAG markedly diminished whereas DTT did not affect cysteine-induced sulfide release from liver pieces.The results do not support the proposal that hydrogen sulfide plays a role in HPV.

AB - We evaluated the hypothesis that an increase in the hydrogen sulfide concentration in pulmonary artery smooth muscle cells causes hypoxic pulmonary vasoconstriction (HPV) by examining the effects of the sulfide donor cysteine and sulfide-synthesis blockers on HPV in isolated rat intrapulmonary arteries (IPA).Cysteine (1 mM) enhanced HPV and also the contraction to PGF2 and both effects were abolished by the cystathionine  lyase blocker propargylglycine (PAG, 1 mM), which had little or no non-selective effect on contraction at this concentration. Neither PAG nor the cysteine aminotransferase antagonist aspartate affected HPV in normal PSS, or in PSS containing physiological concentrations of cysteine, cystine and glutamate, whereas dithiothreitol (DTT), proposed to enhance HPV by converting mitochondrial thiosulfate to sulfide, instead abolished HPV. PAG markedly diminished whereas DTT did not affect cysteine-induced sulfide release from liver pieces.The results do not support the proposal that hydrogen sulfide plays a role in HPV.

KW - hypoxic pulmonary vasoconstriction

KW - sulphide

U2 - 10.1113/jphysiol.2014.277046

DO - 10.1113/jphysiol.2014.277046

M3 - Article

SN - 0022-3751

VL - 593

SP - 385

EP - 401

JO - The Journal of Physiology

JF - The Journal of Physiology

IS - 2

ER -