Abstract
BackgroundBoth 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.MethodsThis 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.ResultsCSE−/− 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.ConclusionsThis study suggests that cardiac CSE regulates cardiac OTR expression, and this effect might play a role in the regulation of cardiovascular function.
Highlights
Both the hydrogen sulfide/cystathionine-γ-lyase (H2S/CSE) and oxytocin/ oxytocin receptor (OT/OT receptor (OTR)) systems have been reported to be cardioprotective
In a model of acute on chronic disease, we recently showed that post-traumatic systemic hyper-inflammation and acute lung injury (ALI) were aggravated in CSE−/− with pre-traumatic cigarette smoke (CS) exposure when compared to wildtype (WT) littermates [7]
All injured animals used in this study underwent pre-traumatic CS exposure and Blunt chest trauma (Txt)
Summary
Both the hydrogen sulfide/cystathionine-γ-lyase (H2S/CSE) and oxytocin/ oxytocin receptor (OT/OTR) systems have been reported to be cardioprotective. 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. Hydrogen sulfide (H2S) is an important regulator of the cardiovascular system and has been shown to be protective in myocardial ischemia-reperfusion injury (I/R) [1,2,3] and heart failure [4]. In a model of acute on chronic disease, we recently showed that post-traumatic systemic hyper-inflammation and acute lung injury (ALI) were aggravated in CSE−/− with pre-traumatic CS exposure when compared to wildtype (WT) littermates [7]
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