The role of oxytocin in cardiovascular regulation

Studies of body volume expansion have indicated that lesions of the anteroventral third ventricle and median eminence block the release of atrial natriuretic peptide (ANP) into the circulation. Detailed analysis of the lesions showed that activation of oxytocin (OT)-ergic neurons is responsible for ANP release, and it has become clear that activation of neuronal circuitry elicits OT secretion into the circulation, activating atrial OT receptors and ANP release from the heart. Subsequently, we have uncovered the entire functional OT system in the rat and the human heart. An abundance of OT has been observed in the early development of the fetal heart, and the capacity of OT to generate cardiomyocytes (CMs) has been demonstrated in various types of stem cells. OT treatment of mesenchymal stem cells stimulates paracrine factors beneficial for cardioprotection. Cardiovascular actions of OT include: i) lowering blood pressure, ii) negative inotropic and chronotropic effects, iii) parasympathetic neuromodulation, iv) vasodilatation, v) anti-inflammatory activity, vi) antioxidant activity, and vii) metabolic effects. OT actions are mediated by nitric oxide and ANP. The beneficial actions of OT may include the increase in glucose uptake by CMs and stem cells, reduction in CM hypertrophy, oxidative stress, and mitochondrial protection of several cell types. In experimentally induced myocardial infarction in rats, continuous in vivo OT delivery improves cardiac healing and cardiac work, reduces inflammation, and stimulates angiogenesis. Because OT plays anti-inflammatory and cardioprotective roles and improves vascular and metabolic functions, it demonstrates potential for therapeutic use in various pathologic conditions.

The effect of oxytocin antagonist on uterus in response to exogenous oxytocin

This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p>0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.

The effect of oxytocin antagonist on uterus in response to exogenous oxytocin

This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p>0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.