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Coronary artery disease (CAD) is a major cardiovascular disease responsible for high morbidity and mortality worldwide. The major pathophysiological basis of CAD is atherosclerosis in association with varieties of immunometabolic disorders that can suppress oxytocin (OT) receptor (OTR) signaling in the cardiovascular system (CVS). By contrast, OT not only maintains cardiovascular integrity but also has the potential to suppress and even reverse atherosclerotic alterations and CAD. These protective effects of OT are associated with its protection of the heart and blood vessels from immunometabolic injuries and the resultant inflammation and apoptosis through both peripheral and central approaches. As a result, OT can decelerate the progression of atherosclerosis and facilitate the recovery of CVS from these injuries. At the cellular level, the protective effect of OT on CVS involves a broad array of OTR signaling events. These signals mainly belong to the reperfusion injury salvage kinase pathway that is composed of phosphatidylinositol 3-kinase-Akt-endothelial nitric oxide synthase cascades and extracellular signal-regulated protein kinase 1/2. Additionally, AMP-activated protein kinase, Ca 2+ /calmodulin-dependent protein kinase signaling and many others are also implicated in OTR signaling in the CVS protection. These signaling events interact coordinately at many levels to suppress the production of inflammatory cytokines and the activation of apoptotic pathways. A particular target of these signaling events is endoplasmic reticulum (ER) stress and mitochondrial oxidative stress that interact through mitochondria-associated ER membrane. In contrast to these protective effects and machineries, rare but serious cardiovascular disturbances were also reported in labor induction and animal studies including hypotension, reflexive tachycardia, coronary spasm or thrombosis and allergy. Here, we review our current understanding of the protective effect of OT against varieties of atherosclerotic etiologies as well as the approaches and underlying mechanisms of these effects. Moreover, potential cardiovascular disturbances following OT application are also discussed to avoid unwanted effects in clinical trials of OT usages.

Oxytocin (OXT) is a hypothalamic neuropeptide composed of nine amino acids. The functions of OXT cover a variety of social and nonsocial activity/behaviors. Therapeutic effects of OXT on aberrant social behaviors are attracting more attention, such as social memory, attachment, sexual behavior, maternal behavior, aggression, pair bonding, and trust. The nonsocial behaviors/functions of brain OXT have also received renewed attention, which covers brain development, reproduction, sex, endocrine, immune regulation, learning and memory, pain perception, energy balance, and almost all the functions of peripheral organ systems. Coordinating with brain OXT, locally produced OXT also involves the central and peripheral actions of OXT. Disorders in OXT secretion and functions can cause a series of aberrant social behaviors, such as depression, autism, and schizophrenia as well as disturbance of nonsocial behaviors/functions, such as anorexia, obesity, lactation failure, osteoporosis, diabetes, and carcinogenesis. As more and more OXT functions are identified, it is essential to provide a general view of OXT functions in order to explore the therapeutic potentials of OXT. In this review, we will focus on roles of hypothalamic OXT on central and peripheral nonsocial functions.

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Oxytocin (OT) is a nonapeptide mainly produced in the supraoptic and paraventricular nuclei. OT in the brain and blood has extensive functions in both mental and physical activities. These functions are mediated by OT receptors (OTRs) that are distributed in a broad spectrum of tissues with dramatic sexual dimorphism. In both sexes, OT generally facilitates social cognition and behaviors, facilitates parental behavior and sexual activity and inhibits feeding and pain perception. However, there are significant differences in OT levels and distribution of OTRs in men from women. Thus, many OT functions in men are different from women, particularly in the reproduction. In men, the reproductive functions are relatively simple. In women, the reproductive functions involve menstrual cycle, pregnancy, parturition, lactation, and menopause. These functions make OT regulation of women’s health and disease a unique topic of physiological and pathological studies. In menstruation, pre-ovulatory increase in OT secretion in the hypothalamus and the ovary can promote the secretion of gonadotropin-releasing hormone and facilitate ovulation. During pregnancy, increased OT synthesis and preterm release endow OT system the ability to promote maternal behavior and lactation. In parturition, cervix expansion-elicited pulse OT secretion and uterine OT release accelerate the expelling of fetus and reduce postpartum hemorrhage. During lactation, intermittent pulsatile OT secretion is necessary for the milk-ejection reflex and maternal behavior. Disorders in OT secretion can account for maternal depression and hypogalactia. In menopause, the reduction of OT secretion accounts for many menopausal symptoms and diseases. These issues are reviewed in this work.