Rat heart: A site of oxytocin production and action

Abstract

We report here that the rat heart is a site of oxytocin (OT) synthesis and release. Oxytocin was detected in all four chambers of the heart. The highest OT concentration was in the right atrium (2128 ؎ 114 pg͞mg protein), which was 19-fold higher than in rat uterus but 3.3-fold lower than in the hypothalamus. OT concentrations were significantly greater in the right and left atria than in the corresponding ventricles. Furthermore, OT was released into the eff luent of isolated, perfused rat heart (34.5 ؎ 4.7 pg͞min) and into the medium of cultured atrial myocytes. Reverse-phase HPLC purification of the heart extracts and heart perfusates revealed a main peak identical with the retention time of synthetic OT. Southern blots of reverse transcription-PCR products from rat heart revealed gene expression of specific OT mRNA. OT immunostaining likewise was found in atrial myocytes and fibroblasts, and the intensity of positive stains from OT receptors paralleled the atrial natriuretic peptide stores. Our findings suggest that heart OT is structurally identical, and therefore derived from, the same gene as the OT that is primarily found in the hypothalamus. Thus, the heart synthesizes and processes a biologically active form of OT. The presence of OT and OT receptor in all of the heart's chambers suggests an autocrine and͞or paracrine role for the peptide. Our finding of abundant OT receptor in atrial myocytes supports our hypothesis that OT, directly and͞or via atrial natriuretic peptide release, can regulate the force of cardiac contraction.Vasopressin and oxytocin (OT) are synthesized predominantly in the magnocellular neurons of the supraoptic nucleus and paraventricular nucleus as well as in the parvocellular neurons within the paraventricular nucleus as parts of larger precursor molecules (1). The precursors are modified posttranslationally and are transported to the posterior pituitary, where the final bioactive peptide products are stored until they are released into the blood stream. Despite being the first peptide hormone to be characterized and synthesized, the effects of oxytocin long were considered to be restricted to stimulation of uterine contractions during labor and milk ejection during lactation. However, OT is found in equivalent concentrations in the neurohypophysis and plasma of both sexes, which suggests that it also may have other physiological roles (2). Moreover, in the central nervous system, OT-containing axons terminate in several brain stem nuclei known to be involved in cardiovascular control, suggesting a potential role for OT in central cardiovascular regulation (3, 4). Indeed, decreased blood pressure may be observed in response to oxytocin given intracerebroventricularly (5), and the inhibition of brain OT synthesis by an antisense oligonucleotide increased blood pressure in rats (6). In primates or humans, the administration of oxytocin often is associated with a decrease in blood pressure (7,8). Peripherally injected OT decreases mean arterial pressure in rats by unknown mec...

Oxytocin in cardiac ontogeny

“…Interestingly, most transcription factors identified so far in the heart are also present in other muscle cells, and myoblast transplantation to the injured heart improves regional systolic heart function (38). Assuming similarities in the differentiation mechanisms of skeletal and cardiac muscles and the expression (15) of both OT and OTR in these cells (8,37), we can speculate that OT plays a role in cardiac muscle regeneration.…”

“…The first-strand cDNA (5 l) was then used for PCR amplification with OT, OTR, or GAPDH exon-specific oligonucleotide primers in a Robocycler Gradient 40 thermocycler (Stratagene). Conditions for RT-PCR analysis of GAPDH, rat OT, and OTR transcripts (7,8) and mouse OTR (10) have already been described. OTR expression also was investigated in the human heart by using cDNA of Human Cardiovascular System MTC Panel (no.…”

“…7930 mesh 140, Corning). The RIA was developed in our laboratory by using specific antibodies generated against OT nonapeptide (8). Synthetic OT (Peninsula Laboratories) was labeled with Na 125 I by the lactoperoxidase method, and 200 l of sample or standards (0-200 pg) was incubated with 100 l of antibody (1:80,000) for 24 h at 4°C.…”

“…In addition, we have demonstrated that in isolated, perfused hearts, an OT antagonist (OTA) blocks basal ANP release (7), suggesting the presence of local OT in the heart. Further study revealed cardiac OT synthesis (8), with OT being detected in the medium of cultured neonatal rat cardiomyocytes (9).…”

Nitrergic modulation of vasopressin, oxytocin and atrial natriuretic peptide secretion in response to sodium intake and hypertonic blood volume expansion

“…In addition, using polymerase chain reaction (PCR) amplification of cDNA obtained from mRNA of both rat atria and ventricles, the presence of specific transcripts was also demonstrated. The OT and OT receptor transcripts were also shown by in situ hybridization in atrial and ventricular tissues using RT-PCR (22,43). Consequently, OT released from the neural lobe may reach the heart by the circulation to induce ANP release, but the intracardiac OT might also play a paracrine role in stimulating ANP release.…”