Increased Activity of the Intracardiac Oxytocinergic System in the Development of Postinfarction Heart Failure

Abstract

Aim. The present study was designed to test the hypothesis that the development of postinfarction heart failure is associated with a change of activity of the intracardiac oxytocinergic system. Methods. Experiments were performed on male Sprague-Dawley rats subjected to myocardial infarction or sham surgery. Four weeks after the surgery, blood samples were collected and the samples of the left ventricle (LV) and right ventricle (RV) were harvested for evaluation of the mRNA expression (RT-PCR) of oxytocin (OT), oxytocin receptor (OTR), natriuretic peptides, and the level of OT and OTR protein (ELISA). The concentration of N-terminal B-type natriuretic peptide was measured to determine the presence of heart failure. Results. Plasma NT-proBNP concentration was higher in the infarcted rats. In the infarcted rats, the expression of OT mRNA and the OT protein level were higher in the RV. There were no significant differences between infarcted and noninfarcted rats in the expression of OT mRNA and in the OT protein level in the fragments of the LV. In both the left and the right ventricles, OTR mRNA expression was lower but the level of OTR protein was higher in the infarcted rats. Conclusions. In the present study, we indicate that postinfarction heart failure is associated with an increased activity of the intracardiac oxytocinergic system.

Therapeutic Potential of Oxytocin in Atherosclerotic Cardiovascular Disease: Mechanisms and Signaling Pathways

“…OTR was localized in microvessels expressing CD31 marker and co-localized with endothelial NO synthase (eNOS) (Jankowski et al, 2010b). OTR mRNA was found in the vena cava, pulmonary veins, and pulmonary artery with lower levels in the aorta in the rats (Jankowski et al, 2000; Wsol et al, 2016). Thus, OT may modulate cardiac activity by activating OTRs on CVS.…”

“…As previously reviewed (Li et al, 2017), plasma OT levels or hypothalamic OT neuronal activities were significantly increased at the early stage of sepsis, advanced cancer patients, adjuvant arthritis and pancreatic injury, which in turn changed the activity of immune system to initiate immune defense, thereby playing the role of immune surveillance. In CVS, OT plasma levels and the activity of the intracardiac OT system significantly increased at 4 weeks after MI in the rats survived from the coronary artery ligation (Ciosek and Drobnik, 2012); post-infarction heart failure was associated with an increased activity of the intracardiac OTergic system (Wsol et al, 2016). Moreover, MI activates parvocellular OT neurons projecting to the rostral ventral lateral medulla (Roy et al, 2018).…”

“…In response to environmetal challenges, OT in the hypothalamus can be released into the blood stream in various amounts and patterns (Hatton and Wang, 2008; Hou et al, 2016) and modulate activities of the heart and blood vessels by activating OTRs along with intracardiac OT (Wsol et al, 2016). OT has both chronotropic and inotropic effects on cardiac activity, which can protect the heart from I/R-induced myocardial injury by reducing oxygen consumption.…”

“…In rat heart (Wsol et al, 2016), the right atrium has the highest OT concentration (∼2.128 ng/mg protein) (Jankowski et al, 1998), comparable with OT content in the hypothalamus wherein different regions have OT concentrations varying from >0.1∼228 ng/mg protein (Gainer, 2011). Thus, when OT is released from the atrium, dramatic changes in the cardiac activity can be elicited through paracrine functions, in which ANP serves as cardioprotective mediators of OT in the heart.…”

Increased oxytocinergic system activity in the cardiac muscle in spontaneously hypertensive SHR rats

“…To date, the expression of the OT in the heart was described only in normotensive rats [12,23,24]. However, in our previous study, we demonstrated increased expression of OT in the hearts of rats developing post-myocardial infarction heart failure [24], where this effect was potentially associated with the antifibrogenic, antihypertrophic, anti-inflammatory effect resulting in the reduction of myocardial damage [14,15,22]. In the study by Menaouar et al oxytocin and its precursor OT-Gly-Lys-Arg (OT-GKR) blocked endothelin-1-induced cardiac hypertrophy ex vivo by activating cGMP/protein kinase G pathway and the PI3K/Akt pathway, considered essential for physiological growth but also for inhibition of pathological hypertrophy in cardiomyocytes [16,25].…”