Oxytocin Pathways Mediate the Cardiovascular and Behavioral Responses to Substance P in the Rat Brain

Maier, Tanja; Dai, Wenjie; Csikós, Tamás; Jirikowski, Gustav F.; Unger, Thomas; Čulman, Juraj

doi:10.1161/01.hyp.31.1.480

Cited by 23 publications

(18 citation statements)

References 22 publications

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“…In prior studies, OT has been shown to either increase or decrease blood pressure (21,22), which could directly affect atherosclerosis. Therefore, the effects of OT infusion on blood pressure were examined in a separate cohort of C57BL/6 mice implanted with osmotic pumps to deliver 0 μ g/kg/hr, 1 μ g/kg/hr, or 5 μ g/kg/hr OT, and blood pressure was monitored over a 2-week period.…”

Section: Methodsmentioning

confidence: 99%

Oxytocin Attenuates Atherosclerosis and Adipose Tissue Inflammation in Socially Isolated ApoE−/− Mice

Nation

Szeto

Mendez

et al. 2010

Psychosomatic Medicine

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Objective To determine the effect of exogenous oxytocin (OT) administration on inflammation and atherosclerosis in socially isolated apoE−/− mice. Hyperlipidemic animals housed in isolated or stressful social environments display more extensive atherosclerosis than those in an affiliative social environment. The neurohypophyseal peptide OT may be involved in both affiliative social behavior and cardiovascular homeostasis, suggesting a role in mediating the benefits of positive social interactions on atherosclerosis. Methods A total of 43, 12-week-old, apoE−/− mice were surgically implanted with osmotic minipumps containing OT (n = 23) or vehicle (n = 20). Blood samples were taken at baseline and after 6 weeks and 12 weeks of treatment. After 12 weeks of treatment, animals were killed, and samples of adipose tissue were dissected from a subset of OT-treated (n = 12) and vehicle-treated (n = 12) animals and incubated in culture media for 6 hours. Media samples were analyzed for interleukin (IL)-6 concentration corrected by sample dry weight. Aortas were dissected, formalin-fixed, and stained with oil-red O for en face quantification of lesion area. t tests were used to compare group means on measures of percent lesion area and IL-6 concentrations. Results There were no group differences in plasma lipids. Adipose tissue samples taken from OT-treated animals secreted significantly less IL-6 over 6 hours (p < .01). OT-treated animals displayed significantly less atherosclerosis in the thoracic aorta (p < .05). Conclusions These results indicate that peripheral OT administration can inhibit atherosclerotic lesion development and adipose tissue inflammation, suggesting a potential role for this neuropeptide in mediating the benefits of stable group housing on atherosclerosis.

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Section: Methodsmentioning

confidence: 99%

Oxytocin Attenuates Atherosclerosis and Adipose Tissue Inflammation in Socially Isolated ApoE−/− Mice

Nation

Szeto

Mendez

et al. 2010

Psychosomatic Medicine

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“…Intracerebroventricularly injected OT decreased blood pressure, whereas inhibition of brain OT synthesis by an anti-sense oligonucleotide increased blood pressure in rats (6). In primates, humans, and rats the administration of oxytocin is often associated with a decrease in blood pressure (7,8).…”

Section: Introductionmentioning

confidence: 99%

Oxytocin is a cardiovascular hormone

Gutkowska

Jankowski

Mukaddam‐Daher

et al. 2000

Braz J Med Biol Res

157

108

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Oxytocin (OT), a nonapeptide, was the first hormone to have its biological activities established and chemical structure determined. It was believed that OT is released from hypothalamic nerve terminals of the posterior hypophysis into the circulation where it stimulates uterine contractions during parturition, and milk ejection during lactation. However, equivalent concentrations of OT were found in the male hypophysis, and similar stimuli of OT release were determined for both sexes, suggesting other physiological functions. Indeed, recent studies indicate that OT is involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of cardiovascular functions. It has long been known that OT induces natriuresis and causes a fall in mean arterial pressure, both after acute and chronic treatment, but the mechanism was not clear. The discovery of the natriuretic family shed new light on this matter. Atrial natriuretic peptide (ANP), a potent natriuretic and vasorelaxant hormone, originally isolated from rat atria, has been found at other sites, including the brain. Blood volume expansion causes ANP release that is believed to be important in the induction of natriuresis and diuresis, which in turn act to reduce the increase in blood volume. Neurohypophysectomy totally abolishes the ANP response to volume expansion. This indicates that one of the major hypophyseal peptides is responsible for ANP release. The role of ANP in OT-induced natriuresis was evaluated, and we hypothesized that the cardio-renal effects of OT are mediated by the release of ANP from the heart. To support this hypothesis, we have demonstrated the presence and synthesis of OT receptors in all heart compartments and the vasculature. The functionality of these receptors has been established by the ability of OT to induce ANP release from perfused heart or atrial slices. Furthermore, we have shown that the heart and large vessels like the aorta and vena cava are sites of OT synthesis. Therefore, locally produced OT may have important regulatory functions within the heart and vascular beds. Such functions may include slowing down of the heart or the regulation of local vascular tone. Correspondence

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“…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).…”

mentioning

confidence: 99%

Rat heart: A site of oxytocin production and action

Jankowski

Hajjar

Kawas

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

171

133

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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...

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Oxytocin Pathways Mediate the Cardiovascular and Behavioral Responses to Substance P in the Rat Brain

Cited by 23 publications

References 22 publications

Oxytocin Attenuates Atherosclerosis and Adipose Tissue Inflammation in Socially Isolated ApoE−/− Mice

Oxytocin Attenuates Atherosclerosis and Adipose Tissue Inflammation in Socially Isolated ApoE−/− Mice

Oxytocin is a cardiovascular hormone

Rat heart: A site of oxytocin production and action

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