Maria Petersson

Oxytocin Causes a Long-Term Decrease of Blood Pressure in Female and Male Rats

The aim of the present study was to investigate the long-term effects of oxytocin (OXY) on blood pressure (BP) and heart rate (HR) in conscious female and male rats. For this purpose, subcutaneous (SC) (0.01, 0.1, and 1 mg/kg) or intracerebroventricular (ICV) (1 microgram/kg) injections of OXY were given during 5-day periods. BP and HR were measured daily. A significant decrease in BP, without affecting HR, compared to saline-treated controls was seen in response to 0.1 (males: p < 0.01, females: p < 0.001) and 1 mg/kg (p < 0.001) of OXY given SC. BP gradually returned to preexperimental levels within 10 days after the last injection in male rats but, in females, the significant lowering of BP remained unchanged during this period. Also OXY ICV (1 microgram/kg) decreased BP (p < 0.05 after one day, p < 0.001 after 5 days of injections). This effect was still present 8 days after the last injection (p < 0.05). These results indicate that OXY may induce a long-term lowering of BP.

Oxytocin causes a sustained decrease in plasma levels of corticosterone in rats

The aim of this study was to investigate how oxytocin (OXT) influences plasma levels of ACTH and corticosterone in rats. A single injection of OXT (1 mg/kg s.c.) caused a transient increase in ACTH and corticosterone. In contrast, 1 mg/kg OXT (but not 10-100 microg/kg) decreased corticosterone, but not ACTH levels, 6 h after the injection. OXT (1 mg/kg s.c.) administered once a day for 5 days, decreased cortiocosterone for 10 days after the last injection. An acute challenge with ACTH increased corticosterone to the same level in rats pretreated with OXT and controls. Dexamethasone decreased corticosterone to equal levels in both groups. Thus, OXT seems to be able to stimulate as well as to inhibit the activity within the HPA-axis within a short- and a long-term perspective, respectively.

Oxytocin increases nociceptive thresholds in a long-term perspective in female and male rats☆

Oxytocin (0.1 and 1.0 mg/kg s.c.) given to male rats during 5 days, increased tail-flick latency when measured 1 (P < 0.05) and 7 days (0.1 mg/kg, P < 0.05; 1.0 mg/kg, P < 0.01) after the last injection. The effect was gone 2 weeks after the end of the treatment. If an additional injection of oxytocin was given 10 days after a previous 5 day treatment period, the significant difference persisted after 3 weeks (P < 0.05). Tail-flick latency was significantly delayed also in oxytocin-treated females when measured 1 week after the treatment period (P < 0.05). Naloxone, but not an oxytocin antagonist, temporarily antagonised the oxytocin induced delay in withdrawal latency. This indicates that oxytocin may act by increasing the activity of opioid mechanisms.

Oxytocin decreases carrageenan induced inflammation in rats

The effects of oxytocin on carrageenan-induced inflammation in rat hindpaw was examined. Oxytocin at 100 (P < 0.05) and 1000 microg/kg s.c. (P < 0.05), but not at 1 and 10 microg/kg s.c., reduced the edema of the paw when measured up to 10 h after the injection. An additional experiment showed that the effect was comparable to the effect of the glucocorticoid dexamethasone. No effect was found by oxytocin i.c.v. In addition, rats with carrageenan-induced inflammation given oxytocin (1000 microg/kg s.c.) responded differently to nociceptive mechanical stimulation (P < 0.05) and had a reduced amount of myeloperoxidase (marker for neutrophil recruitment) in the paw (P < 0.01).

Postnatal Oxytocin Injections Cause Sustained Weight Gain and Increased Nociceptive Thresholds in Male and Female Rats

The aim of the present study was to investigate possible long-term effects of postnatally administered oxytocin on weight gain, gastrointestinal hormone levels, and nociceptive thresholds in rats. For this purpose, s.c. daily injections of oxytocin (1 mg/kg) or saline (NaCl, 0.9%) were given to male and female rat pups on d 10-14 after birth. The animals were killed at the age of 60 or 94 d. Treatment with oxytocin resulted in higher body weight in males, 60 d after birth, and in females from d 60 and throughout the rest of the experiment, compared with controls. The higher body weight was due to an increased weight gain in oxytocin-treated rats, compared with controls, which was most pronounced between 40 and 60 d after birth. Oxytocin-treated male rats had increased circulating levels of cholecystokinin, a tendency to increased plasma levels of insulin (p = 0.066), and relatively more adipose tissue in the thigh and interscapular region, compared with controls. At the age of 60 d, oxytocin-treated female and male rats had a prolonged withdrawal latency when measured in the tail-flick test, compared with controls. This study shows that oxytocin can induce long-lasting changes in weight gain, hormone levels, and nociceptive thresholds, when administered postnatally, in female and male rats.

Postnatal oxytocin treatment and postnatal stroking of rats reduce blood pressure in adulthood

The aim of the present study was to investigate the effects of postnatal oxytocin (OT) treatment and postnatal stroking on blood pressure and heart rate in adult rats. For this purpose, rats were treated subcutaneously with OT (1 mg/kg) once a day on days 1-14 after birth, or exposed to stroking on the ventral side of the abdomen for 5 min once a day on days 1-7 after birth. Blood pressure and heart rate were measured at the age of 7-8 months. The OT-treated male rats had a significantly reduced diastolic blood pressure in adulthood (p < 0.001), and in the female rats, both systolic (p < 0.01) and diastolic blood pressures (p < 0.001) were significantly lower compared to controls given saline postnatally. OT reduced blood pressure also in prenatally stressed female rats, which had a significantly higher blood pressure in adulthood compared to control rats that had not been exposed to prenatal stress. Also, the postnatal stroking reduced diastolic blood pressure in adulthood (p < 0.05). No changes in heart rate were found. In conclusion, both postnatal OT treatment and postnatal stroking reduced blood pressure in adulthood. In addition, in female rats, OT reduced the increase in blood pressure caused by prenatal stress.

Short-term increase and long-term decrease of blood pressure in response to oxytocin-potentiating effect of female steroid hormones

To investigate how the effects of oxytocin on blood pressure are influenced by female sex hormones, oxytocin (1 mg/kg, s.c.) was given to intact cycling and ovariectomized (OVX) female rats. Oxytocin caused a transient increase in blood pressure, most pronounced during proestrus (p < 0.01) and estrus (p < 0.01). This increase was partially antagonized by an oxytocin antagonist. When oxytocin was given for 5 days, blood pressure decreased (intact rats: 123+/-1.5 vs. 130+/-1.3 mm Hg; p < 0.001, OVX rats: 120+/-3.0 vs. 129+/-1.1 mm Hg; p < 0.001). This decrease, not abolished by the oxytocin antagonist, persisted for 3 weeks in intact rats and for 8 days in OVX rats. If oxytocin treatment of OVX rats continued, a nadir of 12 mm Hg (118+/-1.7 mm Hg; p < 0.001) was reached after 8 days. Thereafter heart rate decreased significantly (p < 0.05). One daily oxytocin injection for 12 days to OVX rats decreased blood pressure for 3 weeks, as in intact rats. These results show that acute and chronic oxytocin treatment cause opposite effects on blood pressure, and that these effects are modified by female sex hormones.

Chapter 22 Cardiovascular effects of oxytocin

The well known effects of oxytocin on uterine contraction and milk ejection were found as early as the beginning of the 20th century. Since then many other effects of oxytocin have been found and among them a great number of effects on the cardiovascular system. Oxytocin is released from the neurohypophysis into the circulation and from parvocellular neurons within the paraventricular nucleus (PVN) to many areas within the central nervous system (CNS). Indeed, oxytocin may modify blood pressure as well as heart rate both through effects within the CNS and through effects in other organs, such as the heart, blood vessels and kidney. Oxytocin may also cause cardiovascular effects by affecting other mediators, such as atrial natriuretic peptide (ANP), nitric oxide (NO) and alpha 2-adrenoreceptors.

OXYTOCIN INCREASES THE SURVIVAL OF MUSCULOCUTANEOUS FLAPS

The aim of the present study was to evaluate the effect of oxytocin on survival of musculocutaneous flaps in male Sprague-Dawley rats. For this purpose oxytocin (0.1 or 1.0 mg/kg), an oxytocin antagonist (1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin) (1.0 mg/kg) alone or in combination with oxytocin (1.0 mg/kg) or saline was given subcutaneously (s.c.), 24 hours and 1 hour before and 24 hours after flap surgery. In addition, oxytocin (1 µg/kg) or saline was given intracerebroventricularly (i.c.v.) according to the same schedule. Six days after surgery the amount of viable tissue was measured. Oxytocin 1.0 (but not 0.1) mg/kg s.c. and 1.0 µg/kg i.c.v. increased survival of the flaps (s.c.: 13.8±14.6% versus 6.10±5.45%; p<0.05 and i.c.v.: 25.5±14.0% versus 10.3±5.79%; p<0.01). This effect was abolished by the oxytocin antagonist. Furthermore, the oxytocin-treated rats had significantly higher plasma levels of insulin-like growth factor-1 (IGF-1) (p<0.05). These data indicate that oxytocin increases the survival of musculocutaneous flaps. The effect seems to be exerted within the central nervous system since a 1000 fold lower dose of oxytocin given i.c.v. increased flap survival to the same extent as the s.c. given dose. IGF-1 might be one of the mediators of this effect.

Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation

Oxytocin, a hypothalamic nonapeptide, is linked to increased levels of social interaction, well-being and anti-stress effects. The effects of oxytocin that is released by sensory stimulation during different kinds of interactive behaviors are often underestimated or even forgotten. In fact, many of the positive effects caused during interaction, such a wellbeing, stress reduction and even health promotion, are indeed linked to oxytocin released in response to activation of various types of sensory nerves. Oxytocin is released in response to activation of sensory nerves during labor, breastfeeding and sexual activity. In addition oxytocin is released in response to low intensity stimulation of the skin, e.g., in response to touch, stroking, warm temperature, etc. Consequently oxytocin is not only released during interaction between mothers and infants, but also during positive interaction between adults or between humans and animals. Finally oxytocin is also released in response to suckling and food intake. Oxytocin released in the brain in response to sensory stimulation as a consequence of these types of interactive behaviors, contributes to every day wellbeing and ability to handle stress. Food intake or sex may be used or even abused to achieve oxytocin-linked wellbeing and stress relief to compensate for lack of good relationships or when the levels of anxiety are high. The present review article will summarize the role played by oxytocin released by sensory (in particular somatosensory) stimulation, during various kinds of interactive behaviors. Also the fact that the anti-stress effects of oxytocin are particularly strong when oxytocin is released in response to “low intensity” stimulation of the skin will be highlighted.