Circulating levels of hydrogen sulphide negatively correlate to nitrite levels in gestational hypertensive and preeclamptic pregnant women

Endothelial dysfunction is a hallmark of preeclampsia and the role of nitric oxide (NO) has been extensively studied in this pregnancy complication. In recent years, hydrogen sulphide (H2S) has arisen as a new gasotransmitter with an impact on endothelial function. However, the involvement of H2S in the pathophysiology of preeclampsia is not fully understood, and only a few studies with limited sample size have investigated circulating levels of H2S in preeclamptic patients. Moreover, H2S levels have not been previously evaluated in gestational hypertension. Furthermore, the relationship between H2S and NO in these hypertensive disorders of pregnancy has yet to be determined. We measured H2S levels in plasma of 120 healthy pregnant women, 88 gestational hypertensive and 62 preeclamptic women. We also measured plasma nitrite in a subset of patients and carried out correlation analysis between plasma H2S and nitrite in these three groups. We found that plasma H2S was elevated in preeclampsia and further increased in gestational hypertension compared to healthy pregnancy. Plasma nitrite was reduced in gestational hypertension and preeclampsia, and these levels were negatively correlated with H2S in both gestational hypertension and preeclampsia, but not in healthy pregnancy. Our results indicate that increases in H2S may represent a mechanism triggered as an attempt to compensate reduced NO in gestational hypertension and preeclampsia. Future studies are warranted to investigate the mechanisms underlying H2S/NO interaction on mediating endothelial dysfunction in these hypertensive disorders of pregnancy.

[1]  J. Latorre,et al.  Morbidly obese subjects show increased serum sulfide in proportion to fat mass , 2020, International Journal of Obesity.

[2]  C. Kevil,et al.  Hydrogen sulfide stimulates xanthine oxidoreductase conversion to nitrite reductase and formation of NO , 2020, Redox biology.

[3]  D. Boeldt,et al.  Maternal disease and gasotransmitters. , 2020, Nitric oxide : biology and chemistry.

[4]  Hai-Jian Sun,et al.  Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide , 2020, Frontiers in Pharmacology.

[5]  J. Hart Vasorelaxation elicited by endogenous and exogenous hydrogen sulfide in mouse mesenteric arteries , 2019, Naunyn-Schmiedeberg's Archives of Pharmacology.

[6]  K. Hurt,et al.  Gasotransmitters in pregnancy: from conception to uterine involution† , 2019, Biology of Reproduction.

[7]  K. M. Muraleedharan,et al.  Rapid measurement of hydrogen sulphide in human blood plasma using a microfluidic method , 2019, Scientific Reports.

[8]  T. Simoncini,et al.  Nitric oxide and the biology of pregnancy. , 2018, Vascular pharmacology.

[9]  J. B. Vicente,et al.  Hydrogen Sulfide Biochemistry and Interplay with Other Gaseous Mediators in Mammalian Physiology , 2018, Oxidative medicine and cellular longevity.

[10]  F. Mosca,et al.  Vasomotor effects of hydrogen sulfide in human umbilical vessels. , 2017, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[11]  M. Wareing,et al.  Comparisons between perivascular adipose tissue and the endothelium in their modulation of vascular tone , 2017, British journal of pharmacology.

[12]  Rui Wang,et al.  3-Mercaptopyruvate Sulfurtransferase, Not Cystathionine β-Synthase Nor Cystathionine γ-Lyase, Mediates Hypoxia-Induced Migration of Vascular Endothelial Cells , 2017, Front. Pharmacol..

[13]  R. d'Emmanuele di Villa Bianca,et al.  The Role of the Hydrogen Sulfide Pathway in Male and Female Urogenital System in Health and Disease. , 2017, Antioxidants & redox signaling.

[14]  G. Zagli,et al.  Vasodilator activity of hydrogen sulfide (H2S) in human mesenteric arteries. , 2017, Microvascular research.

[15]  J. Bełtowski,et al.  Hydrogen Sulfide in the Adipose Tissue—Physiology, Pathology and a Target for Pharmacotherapy , 2016, Molecules.

[16]  R. Khalil,et al.  Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia. , 2016, Advances in pharmacology.

[17]  Lei Cao,et al.  H2S induces vasoconstriction of rat cerebral arteries via cAMP/adenylyl cyclase pathway. , 2015, Toxicology and applied pharmacology.

[18]  Asif Ahmed,et al.  The role of H2S bioavailability in endothelial dysfunction. , 2015, Trends in pharmacological sciences.

[19]  G. Osol,et al.  Perivascular Adipose Tissue , 2015, Reproductive Sciences.

[20]  Y. Nishijima,et al.  H2S in the Vasculature: Controversy of Mechanisms in Physiology, Pathologyand Beyond , 2015 .

[21]  S. Karumanchi,et al.  Hydrogen sulfide: a role in vascular physiology and pathology , 2015 .

[22]  D. Tsikas,et al.  Letter by Tsikas and Cooper regarding article, "dysregulation of hydrogen sulfide (H2S) producing enzyme cystathionine γ-lyase (CSE) contributes to maternal hypertension and placental abnormalities in preeclampsia". , 2014, Circulation.

[23]  G. Fink,et al.  Perivascular adipose tissue contains functional catecholamines , 2014, Pharmacology research & perspectives.

[24]  A. Shennan,et al.  Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. , 2015, Obstetrics and gynecology.

[25]  Lubo Zhang,et al.  Potassium channels and uterine vascular adaptation to pregnancy and chronic hypoxia. , 2013, Current vascular pharmacology.

[26]  Mark R. Miller,et al.  Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine &ggr;-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia , 2013, Circulation.

[27]  Guangdong Yang,et al.  Crosstalk between hydrogen sulfide and nitric oxide in endothelial cells , 2013, Journal of cellular and molecular medicine.

[28]  G. Duarte,et al.  Assessment of oxidative status markers and NO bioavailability in hypertensive disorders of pregnancy , 2013, Journal of Human Hypertension.

[29]  D. Wing,et al.  Nitric Oxide and Carbon Monoxide Production and Metabolism in Preeclampsia , 2013, Reproductive Sciences.

[30]  J. Kingdom,et al.  Reduced Cystathionine γ-Lyase and Increased miR-21 Expression Are Associated with Increased Vascular Resistance in Growth-Restricted Pregnancies , 2013, The American journal of pathology.

[31]  T. Yoshimoto,et al.  Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells. , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[32]  F. Crispi,et al.  Dysregulation of hydrogen sulfide producing enzyme cystathionine , 2013 .

[33]  S. Bir,et al.  Analytical measurement of discrete hydrogen sulfide pools in biological specimens. , 2012, Free radical biology & medicine.

[34]  D. Raymond,et al.  A Critical Review of Early-Onset and Late-Onset Preeclampsia , 2011, Obstetrical & gynecological survey.

[35]  M. Whiteman,et al.  Regulation of heart function by endogenous gaseous mediators-crosstalk between nitric oxide and hydrogen sulfide. , 2011, Antioxidants & redox signaling.

[36]  C. Coletta,et al.  Hydrogen Sulfide-Induced Dual Vascular Effect Involves Arachidonic Acid Cascade in Rat Mesenteric Arterial Bed , 2011, Journal of Pharmacology and Experimental Therapeutics.

[37]  D. Julian,et al.  Hydrogen Sulfide Increases Nitric Oxide Production from Endothelial Cells by an Akt-Dependent Mechanism , 2011, Front. Physio..

[38]  M. Suematsu,et al.  Interactions of multiple gas-transducing systems: hallmarks and uncertainties of CO, NO, and H2S gas biology. , 2010, Antioxidants & redox signaling.

[39]  A. Tangerman,et al.  Measurement and biological significance of the volatile sulfur compounds hydrogen sulfide, methanethiol and dimethyl sulfide in various biological matrices. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[40]  P. Moore,et al.  Actions and interactions of nitric oxide, carbon monoxide and hydrogen sulphide in the cardiovascular system and in inflammation--a tale of three gases! , 2009, Pharmacology & therapeutics.

[41]  Yi-Zhun Zhu,et al.  Cardioprotective effect of hydrogen sulfide in ischemic reperfusion experimental rats and its influence on expression of survivin gene. , 2009, Biological & pharmaceutical bulletin.

[42]  J. Tanus-Santos,et al.  Nitric Oxide Formation Is Inversely Related to Serum Levels of Antiangiogenic Factors Soluble Fms-Like Tyrosine Kinase-1 and Soluble Endogline in Preeclampsia , 2008, Hypertension.

[43]  Rui Wang,et al.  Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats. , 2004, American journal of physiology. Heart and circulatory physiology.

[44]  O. Lev,et al.  On-line electrochemical–mass spectrometry study of the mechanism of oxidation of N,N-dimethyl-p-phenylenediamine in aqueous electrolytes , 2004 .

[45]  J. Roberts,et al.  Endothelial Dysfunction in Preeclampsia , 1998, Seminars in reproductive endocrinology.

[46]  K. Abe,et al.  The possible role of hydrogen sulfide as an endogenous neuromodulator , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  L. Cassis,et al.  Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. , 1991, Clinical and experimental hypertension. Part A, Theory and practice.