AUTOCRINE OXYTOCIN ACTION IN CARDIOMYOCYTES: DUAL STIMULATION OF ANP SECRETION AND NITRIC OXIDE-DEPENDENT INHIBITION

Abstract

Historically known for its effects on the reproductive system, oxytocin (OT) is now known to contribute to the regulation of cardiovascular and electrolyte homeostasis. OT is produced in the supraoptic and paraventricular nuclei of the hypothalamus and released into the plasma from neural terminals in the posterior pituitary. However, many studies have identified extracerebral sites of OT production, including the heart and vascular endothelium. Activation of its receptors on endothelial cells, as well as in the hypothalamic/pituitary and cardiac systems, can result in the production of nitric oxide (NO). The present study aimed to investigate the role of NO in the regulation of OT-stimulated atrial natriuretic peptide (ANP) secretion in primary cultures of mouse embryo cardiomyocytes. For this purpose, hearts from Balb C mouse embryos, 19 to 21 days of intrauterine life, were isolated and cultured for assays with OT and other substances that interfere with the synthesis of NO and its second messenger cGMP. The addition of increasing concentrations of OT (0.1, 1, 10, and 100 µM) induced a proportional increase in the secretion of ANP and nitrate into the medium, confirming the stimulatory action of OT in cardiomyocytes. The blockade of ANP release stimulated by OT (10 µM) was observed after the addition of Ornithine Vasotocin (CVI-OVT) (100 µM), a specific OT antagonist. This antagonist inhibited basal ANP secretion when added individually, suggesting that OT may act via an autocrine, tonic stimulatory mechanism on ANP secretion. Amplification of OT-stimulated ANP secretion (10 µM) was observed after its combination with L-NAME, a nitric oxide synthase (NOS) inhibitor (600 µM), and ODQ (100 µM), a soluble guanylate cyclase inhibitor, suggesting the occurrence of nitrergic negative feedback on OT-stimulated ANP release in cardiomyocytes. The results obtained demonstrated nitrergic inhibitory modulation of OT-stimulated ANP secretion.

DOI:https://doi.org/10.56238/sevened2025.031-024