Parenteral Na2S, a fast-releasing H2S donor, but not GYY4137, a slow-releasing H2S donor, lowers blood pressure in rats

• Authors: Adrian Drapala , Dominik Koszelewski , Lenka Tomasova , Ryszard Ostaszewski , Marian Grman , Karol Ondrias , Marcin Ufnal
• Languages of publication: EN

Abstracts

EN

Hydrogen sulfide (H2S) is involved in blood pressure regulation. We evaluated hemodynamic effects of Na2S and morpholin-4-ium (4-methoxyphenyl)(morpholino)phosphinodithioate (GYY4137), H2S donors. GYY4137 is the most widely studied slow-releasing H2S donor, however, its ability to release H2S under physiological conditions is unclear. Hemodynamics were recorded in anaesthetized Wistar-Kyoto rats at baseline and after intravenous (IV) or intraperitoneal (IP) administration of either a vehicle (20% dimethyl sulfoxide), GYY4137 or Na2S. The 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. Similarly, 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 GYY4137 does not exert a hemodynamic effect in Wistar-Kyoto rats. This seems to be due to the high stability of GYY4137 at physiological pH. Therefore, it is likely that widely reported biological effects of GYY4137 are not H2S-dependent but may depend on GYY4137 itself. However, the H2S-dependent biological effects of GYY4137 may be expected in tissues characterized by low pH.

Keywords

EN

hydrogen sulfide; H2S-donor; GYY4137; sodium sulfide; blood pressure; gaseous transmitter

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2017
• Volume: 64
• Issue: 3
• Pages: 561-566

Dates

published

2017

received

2017-03-18

revised

2017-04-25

accepted

2017-04-26

(unknown)

2017-07-27

Contributors

author

Adrian Drapala

• Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland

author

Dominik Koszelewski

• Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland

author

Lenka Tomasova

• Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
• Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic
• Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic

author

Ryszard Ostaszewski

• Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland

author

Marian Grman

• Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic

author

Karol Ondrias

• Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic

author

Marcin Ufnal

• Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland

References

• 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. Med Chem Comm 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. W Z Anal Chem 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: 973-984. 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: 350-354. 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: 6456-6480. 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, Deng LW (2014) Utilizing hydrogen sulfide as a novel anti-cancer agent by targeting cancer glycolysis and pH imbalance. Br J Pharmacol 171: 4322-4336. doi: 10.1111/bph.12773.
• Lee ZW, Zhou J, Chen CS, Zhao Y, Tan CH, Li L, 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: 2351-2360. 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: 187-195. 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: 5501-5511. 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: 457-464. doi: 10.1038/nchembio.1834.
• 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. doi: 10.1016/0003-2697(77)90413-4.
• Park CM, Zhao Y, Zhu Z, Pacheco A, Peng B, Devarie-Baez NO, Bagdon P, Zhang H, Xian M (2013) Synthesis and evaluation of phosphorodithioate-based hydrogen sulfide donors. Mol Biosyst 9: 2430-2434. 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: 1021-1031. 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: 751-758. 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: 329-345. 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: 2514-2522. doi: 10.1161/CIRCULATIONAHA.113.001631.
• Ward FW, Coates ME (1987) Gastrointestinal pH measurement in rats: influence of the microbial flora, diet and fasting. Lab Anim 21: 216-222. doi: 10.1258/002367787781268693.
• 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: 2282-2284. 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-H614. 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-L415. 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: 367-377. doi: 10.1016/j.apsb.2015.06.004.

Identifiers

DOI

10.18388/abp.2017_1569