Parenteral Na2S, a fast-releasing H2S donor, but not GYY4137, a slow-releasing H2S donor, lowers blood pressure in rats.
Hydrogen sulfide (H2S) is involved in blood pressure (BP) regulation. We evaluated hemodynamic effects of Na2S, a fast-releasing H2S donor and GYY4137, a slow-releasing H2S donor. Hemodynamics were recorded in anesthetized Wistar-Kyoto rats at baseline and after intravenous (IV) or intraperitoneal (IP) administration of either a vehicle (20% DMSO) or GYY4137 or Na2S. Stability of GYY4137 in buffers and in plasma was evaluated with nuclear magnetic resonance. The vehicle as well as GYY4137 given IV did not affect mean arterial blood pressure (MABP), whereas Na2S produced a significant decrease in MABP. Similar, IP given Na2S but not GYY4137 lowered MABP. In the buffers at pH of 7.4 and 5.5 and in rat plasma no reaction of GYY4137 was found during 18 hours of observation. In contrast, rapid decomposition of GYY4137 occurred in buffers at pH 2.0. In conclusion, parenteral Na2S but not GYY4137 exerts a hypotensive effect in rats. The lack of hemodynamic effects of GYY4137 may result from its high stability at plasma pH. Since the release of H2S from GYY4137 requires low pH, the biological effects of GYY4137 may be expected in tissues characterized by low pH e.g. in the stomach, and after oral rather than parenteral administration.
Alexander BE, Coles SJ, Fox BC, Khan TF, Maliszewski J, Perry A, Pitak MB, Whiteman M, Wood ME (2015) Investigating the generation of hydrogen sulfide from the phosphonamidodithioate slow-release donor GYY4137. MedChemComm 6: 1649-1655. doi 10.1039/C5MD00170F
Bode H, Arnswald W (1962) Untersuchungen über substituierte Dithiophosphate - II. Mitteilung Bildung der Metall-Diäthyldithiophosphate und ihre Extrahierbarkeit aus mineralsauren Lösungen. Fresenius' Zeitschrift für Analytische Chemie 185: 179-201. doi 10.1007/BF00470785
Bucci M, Papapetropoulos A, Vellecco V, Zhou Z, Zaid A, Giannogonas P, Cantalupo A, Dhayade S, Karalis KP, Wang R, Feil R, Cirino G (2012) cGMP-dependent protein kinase contributes to hydrogen sulfide-stimulated vasorelaxation. PLoS One 7: e53319. doi 10.1371/journal.pone.0053319
Chan J, Dodani SC, Chang CJ (2012) Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. Nat Chem 4: 973-84. doi 10.1038/nchem.1500
Chitnis MK, Njie-Mbye YF, Opere CA, Wood ME, Whiteman M, Ohia SE (2013) Pharmacological actions of the slow release hydrogen sulfide donor GYY4137 on phenylephrine-induced tone in isolated bovine ciliary artery. Exp Eye Res 116: 350-4. doi 10.1016/j.exer.2013.10.004
Drobná M, Misak A, Holland T, Kristek F, Grman M, Tomasova L, Berenyiova A, Cacanyiova S, Ondrias K (2015) Captopril partially decreases the effect of H(2)S on rat blood pressure and inhibits H(2)S-induced nitric oxide release from S-nitrosoglutathione. Physiol Res 64: 479-86.
Feng W, Teo XY, Novera W, Ramanujulu PM, Liang D, Huang D, Moore PK, Deng LW, Dymock BW (2015) Discovery of New H2S Releasing Phosphordithioates and 2,3-Dihydro-2-phenyl-2-sulfanylenebenzo[d][1,3,2]oxazaphospholes with Improved Antiproliferative Activity. J Med Chem 58: 6456-80. doi 10.1021/acs.jmedchem.5b00848
Kashfi K, Olson KR (2013) Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras. Biochem Pharmacol 85: 689-703. doi 10.1016/j.bcp.2012.10.019
Lee ZW, Teo XY, Tay EY, Tan CH, Hagen T, Moore PK, et al. 2014. Utilizing hydrogen sulfide as a novel anti-cancer agent by targeting cancer glycolysis and pH imbalance. Br J Pharmacol. 171(18):4322-36.
Lee ZW, Teo XY, Tay EY, Tan CH, Hagen T, Moore PK, Deng LW (2011) The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo. PLoS One. 6: e21077. doi 10.1111/bph.12773
Li L, Whiteman M, Guan YY, Neo KL, Cheng Y, Lee SW, Zhao Y, Baskar R, Tan CH, Moore PK (2008) Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide. Circulation 117: 2351-60. doi 10.1161/CIRCULATIONAHA.107.753467
Lilyanna S, Peh MT, Liew OW, Wang P, Moore PK, Richards AM, Martinez EC (2015) GYY4137 attenuates remodeling, preserves cardiac function and modulates the natriuretic peptide response to ischemia. J Mol Cell Cardiol 87: 27-37. doi 10.1016/j.yjmcc.2015.07.028
Lin VS, Chang CJ (2012) Fluorescent probes for sensing and imaging biological hydrogen sulfide. Curr Opin Chem Biol 16: 595-601. doi 10.1016/j.cbpa.2012.07.014
Liu Z, Han Y, Li L, Lu H, Meng G, Li X, Shirhan M, Peh MT, Xie L, Zhou S, Wang X, Chen Q, Dai W, Tan CH, Pan S, Moore PK, Ji Y (2013) The hydrogen sulfide donor, GYY4137, exhibits anti-atherosclerotic activity in high fat fed apolipoprotein E(-/-) mice. Br J Pharmacol 169: 1795-809. doi 10.1111/bph.12246
Lohninger L, Tomasova L, Praschberger M, Hintersteininger M, Erker T, Gmeiner BM, Laggner H (2015) Hydrogen sulphide induces HIF-1α and Nrf2 in THP-1 macrophages. Biochimie 112: 187-95. doi 10.1016/j.biochi.2015.03.009
Martelli A, Testai L, Citi V, Marino A, Bellagambi FG, Ghimenti S, Breschi MC, Calderone V (2014) Pharmacological characterization of the vascular effects of aryl isothiocyanates: is hydrogen sulfide the real player? Vascul Pharmacol 60: 32-41. doi 10.1016/j.vph.2013.11.003
Meng G, Ma Y, Xie L, Ferro A, Ji Y (2015) Emerging role of hydrogen sulfide in hypertension and related cardiovascular diseases. Br J Pharmacol 172: 5501-11. doi 10.1111/bph.12900
Mishanina TV, Libiad M, Banerjee R (2015). Biogenesis of reactive sulfur species for signaling by hydrogen sulfide oxidation pathways. Nat Chem Biol 11: 457-64. doi 10.1038/nchembio
Nashef AS, Osuga DT, Feeney RE (1977) Determination of hydrogen sulfide with 5,5'-dithiobis-(2-nitrobenzoic acid), N-ethylmaleimide, and parachloromercuribenzoate. Anal Biochem 79: 394-405.
Park CM, Zhao Y, Zhu Z, Pacheco A, Peng B, Devarie-Baez NO, Bagdon P, Zhangb H, Xian M (2013) Synthesis and evaluation of phosphorodithioate-based hydrogen sulfide donors. Mol Biosyst 9: 2430-4. doi 10.1039/C3MB70145J
Shen X, Pattillo CB, Pardue S, Bir SC, Wang R, Kevil CG (2011) Measurement of plasma hydrogen sulfide in vivo and in vitro. Free Radic Biol Med 50: 1021-31. doi 10.1016/j.freeradbiomed.2011.01.025
Sikora M, Drapala A, Ufnal M (2014) Exogenous hydrogen sulfide causes different hemodynamic effects in normotensive and hypertensive rats via neurogenic mechanisms. Pharmacol Rep 66: 751-8. doi 10.1016/j.pharep.2014.04.004
Tomasova L, Dobrowolski L, Jurkowska H, Wróbel M, Huc T, Ondrias K, Ostaszewski R, Ufnal M (2016) Intracolonic hydrogen sulfide lowers blood pressure in rats. Nitric Oxide 60: 50-58. doi 10.1016/j.niox.2016.09.007
Ufnal M, Sikora M, Szczepanska-Sadowska E (2008) Interleukin-1 receptor antagonist reduces the magnitude of the pressor response to acute stress. Neurosci Lett 448: 47-51. doi 10.1016/j.neulet.2008.10.010
Vasas A, Dóka É, Fábián I, Nagy P (2015) Kinetic and thermodynamic studies on the disulfide-bond reducing potential of hydrogen sulfide. Nitric Oxide 46: 93-101. doi 10.1016/j.niox.2014.12.003
Wallace JL, Wang R (2015) Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous gasotransmitter. Nat Rev Drug Discov 14: 329-45. doi 10.1016/j.niox.2014.12.003
Wang R (2012) Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiol Rev 92: 791-896. doi 10.1152/physrev.00017.2011
Wang K, Ahmad S, Cai M, Rennie J, Fujisawa T, Crispi F, Baily J, Miller MR, Cudmore M, Hadoke PW, Wang R, Gratacós E, Buhimschi IA, Buhimschi CS, Ahmed A (2013) Dysregulation of hydrogen sulfide producing enzyme cystathionine γ-lyase contributes to maternal hypertension and placental abnormalities in preeclampsia. Circulation 127: 2514-22. doi 10.1161/CIRCULATIONAHA
Ward FW, Coates ME (1987) Gastrointestinal pH measurement in rats: influence of the microbial flora, diet and fasting. Lab Anim 21: 216-22.
Xuan W, Sheng C, Cao Y, He W, Wang W (2012) Fluorescent probes for the detection of hydrogen sulfide in biological systems. Angew Chem Int Ed Engl 51: 2282-4. doi 10.1002/anie.201107025
Yoo D, Jupiter RC, Pankey EA, Reddy VG, Edward JA, Swan KW, Peak TC, Mostany R, Kadowitz PJ (2015) Analysis of cardiovascular responses to the H2S donors Na2S and NaHS in the rat. Am J Physiol Heart Circ Physiol 309: H605-14. doi 10.1152/ajpheart.00171.2015
Yuan S, Patel RP, Kevil CG (2015) Working with nitric oxide and hydrogen sulfide in biological systems. Am J Physiol Lung Cell Mol Physiol 308: L403-15. doi: 10.1152/ajplung.00327.2014
Zheng Y, Ji X, Ji K, Wang B (2015) Hydrogen sulfide prodrugs-a review. Acta Pharm Sin B 5: 367-77. doi 10.1016/j.apsb.2015.06.004
Acta Biochimica Polonica is an open access quarterly and publishes four issues a year. All contents are distributed under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) license. Everybody may use the content following terms: Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made, ShareAlike — If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original. There are no additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Copyright for all published papers © stays with the authors.
Copyright for the journal: © Polish Biochemical Society.