Interaction of the hydrogen sulfide system with the oxytocin system in the injured mouse heart

Tamara Merz; Britta Lukaschewski; Daniela Wigger; Aileen Rupprecht; Martin Wepler; Michael Gröger; Clair Hartmann; Matthew Whiteman; Csaba Szabo; Rui Wang; Christiane Waller; Peter Radermacher; Oscar McCook

doi:10.1186/s40635-018-0207-0

Interaction of the hydrogen sulfide system with the oxytocin system in the injured mouse heart

Intensive Care Med Exp. 2018 Oct 19;6(1):41. doi: 10.1186/s40635-018-0207-0.

Authors

Tamara Merz¹, Britta Lukaschewski², Daniela Wigger³, Aileen Rupprecht², Martin Wepler^{2

4}, Michael Gröger², Clair Hartmann^{2

4}, Matthew Whiteman⁵, Csaba Szabo^{6

7}, Rui Wang⁸, Christiane Waller^{3

9}, Peter Radermacher², Oscar McCook²

Affiliations

¹ Institute of Anesthesiological Pathophysiology and Process Engineering, University Medical School, Helmholtzstrasse 8-1, 89081, Ulm, Germany. tamara.merz@uni-ulm.de.
² Institute of Anesthesiological Pathophysiology and Process Engineering, University Medical School, Helmholtzstrasse 8-1, 89081, Ulm, Germany.
³ Clinic for Psychsomatic Medicine and Psychotherapy, University Medical Center, Ulm, Germany.
⁴ Department of Anesthesiology, University Medical Center, Ulm, Germany.
⁵ University of Exeter Medical School, St. Luke's Campus, Exeter, England, UK.
⁶ Chair of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
⁷ Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
⁸ Department of Biology, Laurentian University, Sudbury, ON, Canada.
⁹ Department of Psychosomatic Medicine and Psychotherapy, Paracelsus Medical University, Nuremberg General Hospital, Nuremberg, Germany.

Abstract

Background: Both the hydrogen sulfide/cystathionine-γ-lyase (H₂S/CSE) and oxytocin/oxytocin receptor (OT/OTR) systems have been reported to be cardioprotective. H₂S can stimulate OT release, thereby affecting blood volume and pressure regulation. Systemic hyper-inflammation after blunt chest trauma is enhanced in cigarette smoke (CS)-exposed CSE^-/- mice compared to wildtype (WT). CS increases myometrial OTR expression, but to this point, no data are available on the effects CS exposure on the cardiac OT/OTR system. Since a contusion of the thorax (Txt) can cause myocardial injury, the aim of this post hoc study was to investigate the effects of CSE^-/- and exogenous administration of GYY4137 (a slow release H₂S releasing compound) on OTR expression in the heart, after acute on chronic disease, of CS exposed mice undergoing Txt.

Methods: This study is a post hoc analysis of material obtained in wild type (WT) homozygous CSE^-/- mice after 2-3 weeks of CS exposure and subsequent anesthesia, blast wave-induced TxT, and surgical instrumentation for mechanical ventilation (MV) and hemodynamic monitoring. CSE^-/- animals received a 50 μg/g GYY4137-bolus after TxT. After 4h of MV, animals were exsanguinated and organs were harvested. The heart was cut transversally, formalin-fixed, and paraffin-embedded. Immunohistochemistry for OTR, arginine-vasopressin-receptor (AVPR), and vascular endothelial growth factor (VEGF) was performed with naïve animals as native controls.

Results: CSE^-/- was associated with hypertension and lower blood glucose levels, partially and significantly restored by GYY4137 treatment, respectively. Myocardial OTR expression was reduced upon injury, and this was aggravated in CSE^-/-. Exogenous H₂S administration restored myocardial protein expression to WT levels.

Conclusions: This study suggests that cardiac CSE regulates cardiac OTR expression, and this effect might play a role in the regulation of cardiovascular function.

Keywords: Arginine-vasopressin receptor; Blood glucose; Cardiovascular system; Cystathionine-γ-lyase; GYY4137; Vascular endothelial growth factor.

Abstract

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