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

Ever since the discovery of endogenous H₂S and the identification of its cytoprotective properties, efforts have been made to develop strategies to use H₂S as a therapeutic agent. The ability of H₂S to regulate vascular tone, inflammation, oxidative stress, and apoptosis might be particularly useful in the therapeutic management of critical illness. However, neither the inhalation of gaseous H₂S, nor the administration of inorganic H₂S-releasing salts or slow-releasing H₂S-donors are feasible for clinical use. Na₂S₂O₃ is a clinically approved compound with a good safety profile and is able to release H₂S, in particular under hypoxic conditions. Pre-clinical studies show promise for Na₂S₂O₃ in the acute management of critical illness. A current clinical trial is investigating the therapeutic potential for Na₂S₂O₃ in myocardial infarct. Pre-eclampsia and COVID-19 pneumonia might be relevant targets for future clinical trials.

Today it is well established that early life stress leads to cardiovascular programming that manifests in cardiovascular disease, but the mechanisms by which this occurs, are not fully understood. This perspective review examines the relevant literature that implicates the dysregulation of the gasomediator hydrogen sulfide and the neuroendocrine oxytocin systems in heart disease and their putative mechanistic role in the early life stress developmental origins of cardiovascular disease. Furthermore, interesting hints towards the mutual interaction of the hydrogen sulfide and OT systems are identified, especially with regards to the connection between the central nervous and the cardiovascular system, which support the role of the vagus nerve as a communication link between the brain and the heart in stress-mediated cardiovascular disease.

The purpose of this review is to explore the parallel roles and interaction of hydrogen sulfide (H₂S) and oxytocin (OT) in cardiovascular regulation and fluid homeostasis. Their interaction has been recently reported to be relevant during physical and psychological trauma. However, literature reports on H₂S in physical trauma and OT in psychological trauma are abundant, whereas available information regarding H₂S in psychological trauma and OT in physical trauma is much more limited. This review summarizes recent direct and indirect evidence of the interaction of the two systems and their convergence in downstream nitric oxide-dependent signaling pathways during various types of trauma, in an effort to better understand biological correlates of psychosomatic interdependencies.