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Biomedical subjects

A J Summerlee

Publications and source records attributed to A J Summerlee.

At least 19 recordsLinked to original sources
PubMed2001

Relaxin and drinking in pregnant rats.

Work reported in this chapter describes the potential role of relaxin in resetting cardiovascular thresholds in pregnant rats. Relaxin, a polypeptide produced primarily by the ovary in pregnant animals in many species, is also produced in the brain. Exogenous administration of relaxin into the brain causes a profound drinking response which is negated by pretreatment with a specific monoclonal antibody to rat relaxin when the antibody is injected into the brain. Neutralizing the action of endogenous brain relaxin in pregnant rats also blocks the normal increase in drinking that is observed in rats at night during the second half of pregnancy. Relaxin acts through the forebrain angiotensin system at the level of the subfornical organ (an important interface between the blood, the brain and the cerebrospinal fluid) as blockade of the angiotensin II receptor action negates several central actions of relaxin. Expression of angiotensin II AT1 receptors in the subfornical organ increases in parallel with the increase in circulating relaxin seen in the second half of pregnancy. Neutralizing the effects of endogenous brain relaxin, using central injections of the monoclonal antibody, blocks this increase in the expression of angiotensin II AT1 receptors in subfornical organ. These data imply that relaxin in the brain may act to affect central cardiovascular thresholds in rats and this may be important for the normal physiology of pregnancy.

Animals↗
PubMed1999

Evaluation of the effect of GnRH on follicular ovarian cysts in dairy cows using trans-rectal ultrasonography.

The objectives of this study were to evaluate ovarian changes in cows with follicular ovarian cysts following treatment with either GnRH or saline. The parameters determined were the intervals from treatment to observation of a CL and from treatment to disappearance of the cyst, and the association between serum concentrations of LH, FSH and the LH/FSH ratio, before and after treatment, with the test intervals. Thirty-nine cows were identified as having follicular cysts. The GnRH treatment induced a significant increase in LH and the LH/FSH ratio. The gonadotropin response was not associated with the intervals from treatment to CL detection or to disappearance of the cyst. Survival curves for the intervals from treatment to CL detection and cyst disappearance indicate that treatment with GnRH or saline did not yield significantly different results for either parameter. The results question the efficacy of treating cystic ovarian disease with GnRH.

Animals↗
PubMed1998

Relaxin inhibits the pulsatile release of oxytocin but increases basal concentrations of hormone in lactating rats.

The effects of porcine relaxin were examined in urethane-anesthetized, lactating rats to clarify the actions of relaxin on basal levels and the pulsatile release of oxytocin during suckling. Baseline plasma oxytocin concentrations were 27.6+/-2.9 pM in unsuckled rats. They were significantly increased in rats after the onset of suckling (34.5+/-2.4 pM) compared with unsuckled animals. Oxytocin concentrations were increased further during reflex milk ejection (41.2+/-2.7 pM). Treatment with porcine relaxin (5 microg in 0.1 ml saline) caused a significant (p < 0.05) increase in plasma oxytocin compared with pretreatment concentrations or saline injection in all three groups. Frequent blood samples were taken before and during milk ejection to confirm pulsatile oxytocin associated with reflex milk ejection. Short-lived (5-10-sec) pulses with peak concentrations of oxytocin 392.4+/-122.1 pM were observed shortly before or at the time of the peak rise in intramammary pressure associated with reflex milk ejection. Relaxin (5 microg i.v.) completely suppressed the pulsatile release of oxytocin. These data suggest that relaxin increases basal secretion of oxytocin but inhibits the pulsatile secretion associated with reflex milk ejection.

Animals↗
PubMed1998

Neutralization of relaxin within the brain affects the timing of birth in rats.

Experiments were performed to determine whether neutralization of relaxin in the brain, by injecting monoclonal antibodies to rat relaxin into the ventricular system of the brain, affected either the timing or the processes of birth in rats. Pregnant rats were injected daily through a chronically implanted intracerebroventricular cannula either with a specific monoclonal antibody raised against rat relaxin from days 12-22 of gestation or with an antibody raised against fluorescein as a control. The rats were watched closely from the afternoon of day 20 of pregnancy, and the process of birth was observed. No sign of dystocia was observed in any of the rats in the experiment. Neutralization of endogenous relaxin caused a significant decrease in the length of gestation (505.4 +/- 3.1 h) compared with that in rats treated with PBS (524.6 +/- 0.5 h) or that in rats treated with a nonspecific antibody (525.9 +/- 0.7 h). The time to the onset of delivery was also shorter in the relaxin-neutralized group (507.8 +/- 1.1 h) compared with that in either PBS-treated (526.5 +/- 0.6 h) or fluorescein antibody-treated (525.3 +/- 0.7 h) animals. In contrast, there was no significant effect of the relaxin antibody on length of straining, duration of parturition, delivery interval, live birth rate, or body weight of the neonates. Premature delivery in the relaxin-neutralized group was accompanied by a 24-h advance in the fall in plasma progesterone. These data support the hypothesis that there may be a central relaxin system that is independent of the peripheral relaxin system. Central relaxin may have a significant physiological role on the timing of pregnancy in the rat, but does not affect the course of labor once it has started.

Animals↗
PubMed1998

The dipsogenic effects of rat relaxin: The effect of photoperiod and the potential role of relaxin on drinking in pregnancy.

Experiments were done to examine whether rat relaxin is dipsogenic and whether such dipsogenic effects of rat relaxin are related to time of injection during the light-dark cycle. Female rats were fitted with a chronic intra-cerebro-ventricular (i.c.v.) cannula. Rat relaxin (2.5, 5, 10, 25, 50, or 100 ng/2 microl in 0.9% saline) was injected into the right lateral ventricle at either morning (0800-1000 h), afternoon (1400-1600 h), or night (2200-2400 h), and water consumption was measured. Relaxin caused a dose-dependent dipsogenesis at doses > or = 5 ng, but the sensitivity and magnitude of the response varied with the photoperiod. Water consumption was smallest (3.5 +/- 0.7 ml at 50 ng) and least sensitive (minimal effective dose at 25 ng) in the afternoon and maximal (17.7 +/- 2.3 ml at 50 ng) and most sensitive (minimal effective dose 5 ng) at night. The latency from injection to drinking was 55.8 +/- 10.4 sec (mean +/- SEM) and did not vary significantly with either the dose or time of day. A second set of experiments was done to examine the effects of neutralizing the central actions of relaxin on drinking behavior in pregnancy. Pregnant rats were injected daily, through a chronically implanted i.c.v. cannula, with either a specific monoclonal antibody raised against rat relaxin from day 12 to day 22 of gestation or with saline as a control. Drinking and eating behavior and weight gain were monitored every 12 h during pregnancy. There was a significant decrease in water consumed at night, but no effect on drinking during the day in relaxin-neutralized rats. These animals also showed a decrease in weight gain during pregnancy compared with controls and gave birth to lighter-weight litters. These data provide evidence that the dipsogenic response to exogenous rat relaxin in female rats varies with time of injection during the light-dark cycle and suggest that relaxin in the brain may have a role in nighttime drinking behavior during the second half of pregnancy.

Animals↗
PubMed1998

The cardiovascular effects of porcine relaxin in Brattleboro rats.

The effects of porcine relaxin on arterial blood pressure, heart rate, and the release of vasopressin and oxytocin were investigated in homozygous diabetes insipidus (di/di) Brattleboro and Long-Evans rats. Acute iv injection of relaxin (5 microg) caused a significant increase in mean arterial, systolic and diastolic blood pressures in Long-Evans rats compared with control injections of saline, but had no pressor effect in Brattleboro rats. Circulating concentrations of vasopressin were also significantly elevated above baseline in the Long-Evans rats 1 min after relaxin treatment, but remained undetectable in the relaxin-treated Brattleboro rats. Relaxin increased heart rate in both groups of animals 4 min after injection. The chronotropic effect of relaxin was, however, attenuated in the Brattleboro rats. Intravenous relaxin injection also caused a significant increase in plasma oxytocin concentrations 5 min posttreatment in both the Long-Evans and Brattleboro rats. The change in plasma oxytocin above basal concentrations was significantly greater in Brattleboro rats compared with Long-Evans controls. The data in this study demonstrate that iv relaxin increases heart rate, but not arterial blood pressure in Brattleboro rats. Furthermore, the relaxin-induced release of oxytocin in Brattleboro rats does not result in an acute pressor response.

Animals↗
PubMed1996

Changing effect of i.c.v. IL-1 beta on vasopressin release in anaesthetized, female rats at different stages of lactation: role of prostaglandins and noradrenaline.

Interleukin-1 beta stimulates oxytocin and vasopressin release in conscious, male rats and causes a rise in blood pressure. These experiments were done to : A) examine the effect of i.c.v. interleukin-1 beta (1 ng/microliter) on circulating levels of vasopressin in female rats at different stages of lactation and B) determine if alpha-adrenergic mechanisms and/or prostaglandins were involved as mediators. Urethane-anaesthetized nonlactating rats and rats at Day 7, 10, 20 and 26 of lactation were set up for arterial blood sampling and i.c.v. injections. One mL blood samples were obtained in one min periods before, and at 1, 2.5, 5, 10, 30, 60 and 120 min after the following treatments: i.c.v. treatment with either interleukin-1 beta (1 ng in 1 microliter PBS-BSA) or PBS-BSA (1 microliter) as a vehicle control; or i.c.v. treatment with interleukin-1 beta following pretreatment with either phentolamine (1.7 micrograms/microliter i.c.v.) or indomethacin (1 microgram/microliter i.c.v.). As blood was sampled, isotonic saline was infused (1 mL per min) and blood pressure was monitored to minimize any hypovolemic effects due to sampling. Extracted plasma was assayed using a specific vasopressin radioimmunoassay. Interleukin-1 beta i.c.v. stimulated the release of vasopressin above that elicited by PBS-BSA alone in non-lactating rats resulting in an approximate 1.2 to 2-fold increase in plasma hormone levels. Throughout the first half of lactation, vasopressin responsiveness to i.c.v. interleukin-1 beta treatment was markedly attenuated. In latter stages of lactation, the response recovered and resembled that of non-lactators around the time of weaning. Prostaglandins consistently mediate a stimulatory action of interleukin-1 beta on vasopressin release whereas alpha-adrenergic mechanisms mediate a depression of interleukin-1 beta-induced vasopressin release during the early to middle stages of lactation. It is possible that the depression in interleukin-1 beta-stimulation of vasopressin release in early to mid-lactation is conducive for nursing to occur and that the increase in vasopressin responsiveness towards the latter stages of lactation represents a component of the weaning process.

Anesthesia↗
PubMed1995

The emerging concept of relaxin as a centrally acting peptide hormone with hemodynamic actions.

The novel finding that relaxin has an action on the brain was first published in 1984. Since then, it has been shown that exogenous relaxin affects the release of a number of hypothalamo-pituitary hormones and has a robust pressor action. In this paper, we review the accumulating evidence that relaxin affects the release of oxytocin and vasopressin by an action at the level of the brain. The potential mechanisms of this central action are discussed and the evidence presented for the interaction between relaxin and the forebrain angiotensin-II system. Furthermore, we articulate the possible physiological influences of relaxin on the changes in cardiovascular function that occur during pregnancy.

Animals↗
PubMed1994

Effects of relaxin on blood pressure and the release of vasopressin and oxytocin in anesthetized rats during pregnancy and lactation.

The effects of porcine relaxin (pRXN) on arterial blood pressure and on the release of vasopressin (VP) and oxytocin (OT) were investigated in urethane-anesthetized rats at different stages of pregnancy and lactation. Acute i.v. pRXN (5 micrograms) caused a significant increase in systolic and diastolic blood pressure in pregnant and lactating rats. However, the pressor response was attenuated from Day 14 of pregnancy to Day 1 of lactation. The hormone had no effect on blood pressure in Day 16, Day 19, or Day 21 pregnant rats. At all stages of pregnancy and lactation, i.v. pRXN caused a significant increase in plasma VP concentrations. This response was attenuated in Day 19 and Day 21 pregnant and in Day 1 lactating rats. Intravenous pRXN also caused a significant, short-term increase in plasma OT in pregnant and lactating rats. The OT response to pRXN was attenuated on Day 16 of pregnancy, and pRXN had no effect on plasma OT in late-pregnant rats. The data in this study demonstrate that pRXN causes an increase in both arterial blood pressure and VP and OT release in anesthetized pregnant and lactating rats. However, these effects are either reduced or not observed in late-pregnant and early-lactating rats.

Anesthesia↗
PubMed1994

Brain angiotensin-II partially mediates the effects of relaxin on vasopressin and oxytocin release in anesthetized rats.

Experiments were conducted in anesthetized rats to assess the contribution of the brain angiotensin-II system in the relaxin-induced secretion of vasopressin and oxytocin. Intravenous injection of porcine relaxin (5 micrograms) caused a significant (P < 0.05, by analysis of variance) increase in plasma concentrations of both hormones. Peak concentrations of both vasopressin (75.2 +/- 2.9 pmol/liter) and oxytocin (38.4 +/- 1.2 pmol/liter) were observed 1-2.5 min after relaxin injection. Thereafter, concentrations fell significantly (P < 0.05) but remained elevated for a further 25 minutes. Continuous infusion of a specific angiotensin-II receptor antagonist into the lateral cerebral ventricle did not affect baseline levels of either vasopressin or oxytocin, but did significantly reduce (P < 0.05) the relaxin-induced release of both peptides. A significant (P < 0.05) short term increase in both plasma vasopressin and oxytocin occurred 1 min after injection of 5 micrograms relaxin, iv, in angiotensin-II-antagonized rats, but the concentrations of both neuropeptides were significantly (P < 0.05) lower than those observed in the angiotensin-intact relaxin-treated controls. These data suggest that relaxin may act through the central angiotensin-II system to induce the release of vasopressin and oxytocin.

Anesthesia↗
PubMed1994

Role of the subfornical organ in the relaxin-induced prolongation of gestation in the rat.

The role of the subfornical organ in the timing of birth in the rat was investigated. Animals with radiofrequency lesions of the subfornical organ made on day 12 of pregnancy gave birth significantly earlier (P < 0.05) than intact and control-lesioned rats. Animals with lesions made on day 19 of pregnancy gave birth within control times. In addition, the natural fall in plasma relaxin observed at the end of gestation in rats was prevented by i.v. infusion of porcine relaxin (4.2 micrograms/h for 5 days from day 19 of gestation), which maintained plasma relaxin levels at approximately 100 ng/ml. This rate of infusion was selected because the resultant circulating levels of relaxin reflect plasma concentrations observed on day 20 of pregnancy in rats. The effect of lesion of the subfornical organ was then studied on the timing of birth in relaxin-infused rats. Intact animals and rats with control lesions receiving an infusion of relaxin had significantly (P < 0.05) prolonged pregnancies compared with intact saline-infused controls. However, the timing of birth of rats with lesions of the subfornical organ receiving an infusion of relaxin was not significantly (P > 0.05) different from that in intact saline-infused controls. The results support the hypothesis that the subfornical organ appears to mediate the central effects of relaxin and may have a natural role in the events that lead to delivery in the rat.

Animals↗
PubMed1994

Effects of exogenous relaxin on oxytocin and vasopressin release and the intramammary pressure response to central hyperosmotic challenge.

Experiments were done to study the effects of porcine relaxin on osmotically evoked changes in intramammary pressure and the release of oxytocin and vasopressin in anaesthetized rats. Injections (1 microliter) of hypertonic (0.75 M) NaCl into the left lateral cerebral ventricle were used to induce consistent rises in intramammary pressure and the release of oxytocin and vasopressin. Plasma hormone concentration was determined by radioimmunoassay. Relaxin (5 micrograms i.v.) significantly (P < 0.05) suppressed the intramammary pressure response to osmotic challenge 5 and 10 min after treatment. However, pretreatment with a specific vasopressin V1 receptor antagonist completely negated the effect of relaxin on intramammary pressure. Baseline levels of oxytocin and vasopressin in unstimulated rats were 41 +/- 1.6 and 36 +/- 1.1 pmol/l respectively. Osmotic challenge induced significant (P < 0.05) rises in plasma levels of both hormones (62.8 +/- 1.1 and 67.9 +/- 1.2 pmol/l respectively) which were further augmented by relaxin (81.3 +/- 1.8 and 117.1 +/- 2.4 pmol/l respectively; P < 0.05). The data confirm that central osmotic challenge provokes the release of oxytocin and vasopressin but the effects of oxytocin at the level of the mammary gland may be obscured by the action of vasopressin affecting blood flow to the gland.

Animals↗
PubMed1991

Central angiotensin partially mediates the pressor action of relaxin in anesthetized rats.

Experiments were conducted to investigate the role of the brain angiotensin system in mediating the pressor effects of porcine relaxin in anesthetized female rats. Continuous intracerebroventricular infusion of a specific angiotensin II receptor antagonist (Sar1-Ala8-angiotensin II) completely negated the pressor response to centrally administered relaxin, but only partially suppressed the increase in blood pressure observed after iv injection of the hormone. These results indicate that the pressor effects of relaxin may be mediated, at least in part, by brain angiotensin. Rats with a compromised central angiotensin system were then treated in combination with a peripheral vasopressin (V1) receptor antagonist. Only after both treatments were the pressor effects of iv relaxin completely negated. These data imply that there is also a significant pressor action of relaxin which is independent of the brain angiotensin system. The most likely alternative is a direct action of relaxin on the neural lobe of the pituitary, to provoke the release of vasopressin.

Angiotensin II↗
PubMed1989

Lesion of the subfornical organ affects the haemotensive response to centrally administered relaxin in anaesthetized rats.

Experiments were performed on anaesthetized, lactating rats to investigate the acute central actions of relaxin on blood pressure and vasopressin release. When compared with saline and control injections of isotonic protein extract, administration of relaxin into either the lateral or dorsal portion of the third ventricle caused a significant and sustained rise in arterial blood pressure. In contrast, relaxin administered to the ventral portion of the third ventricle caused only a short-term rise in blood pressure. Injections of relaxin into the fourth ventricle were without significant effect, suggesting that the central actions of relaxin on blood pressure are mediated by receptors restricted to the diencephalon or mesencephalon. A similar ventricular specificity was noted for the central relaxin-induced stimulation of vasopressin release as judged by concentrations of the hormone in the peripheral plasma. It is unlikely that the stimulation of vasopressin release is wholly responsible for the observed pressor effect observed. Lesion of the subfornical organ negated the pressor effect to relaxin injected into the dorsal region of the third ventricle, but did not affect the pressor response observed after injection of relaxin into the ventral portion of the third ventricle. These results demonstrate a biphasic action of centrally administered relaxin, with the response to dorsally placed third ventricle relaxin being mediated by the subfornical organ, and the response to ventral injections associated with an unknown structure of the ventral third ventricle wall.

Animals↗
PubMed1987

Central inhibitory effects of relaxin on the milk ejection reflex of the rat depends upon the site of injection into the cerebroventricular system.

The effects of centrally administered porcine relaxin on the milk-ejection reflex were studied in anaesthetized, lactating rats. Injection of relaxin into either the lateral ventricles (10-1000 ng) or third ventricle (500 ng) of the brain significantly inhibited suckling-induced reflex milk-ejection. Following injection of relaxin into the third ventricle, the onset of inhibition was immediate and more profound compared to injection into the lateral ventricle, after which there was a delay to the onset of inhibition. Relaxin was without effect when injected into the fourth ventricle or cisterna magna, thus suggesting that the site of action was within the diencephalon and the mesencephalon. Because these effects were reversed by naloxone, the central inhibitory action of relaxin appears to be mediated through endogenous opioid peptides.

Animals↗
PubMed1987

Effects of chronic infusion of porcine relaxin on oxytocin release in lactating rats.

The effects of chronic infusion of porcine relaxin on oxytocin release were studied in lactating rats. Infusion of relaxin (4.2 micrograms/h for either 4 or 6 days) suppressed reflex milk ejection and reduced litter weight gain for 48 h compared with saline-infused controls. After 2 days, neither the rate of growth nor the frequency of milk ejection were significantly different from controls. For 24 h after the infusion of relaxin ended, litters gained weight more quickly than controls but there was no difference seen in the frequency of milk ejection. The effects on oxytocin release of stopping an infusion of relaxin after 3 days were investigated. There was a significant (P less than 0.01) rise in plasma oxytocin (up to 90 pmol/l) 30 min after the infusion was stopped, followed by a sustained rise in intramammary pressure. Treatment of relaxin-infused rats with naloxone (0.1 mg/kg) when the infusion was halted caused a more rapid release of oxytocin (within 2 min), a greater release of oxytocin (up to 140 pmol/l) and a prolonged rise in intramammary pressure.

Animals↗
PubMed1987

The subfornical organ and relaxin-induced inhibition of reflex milk ejection in lactating rats.

Experiments were carried out on anaesthetized, lactating rats to investigate the possible role of the subfornical organ in mediating relaxin-induced inhibition of reflex milk ejection. Milk ejection was judged by the behavioural response of the sucklings and by transient rises in intramammary pressure. Radiofrequency lesions of the subfornical organ, or control lesions in adjacent areas of the cerebrum, did not affect the pattern or the magnitude of intramammary pressure changes at reflex milk ejection. Purified porcine relaxin given by either i.v. (5 micrograms) or intracerebroventricular (50 ng) injection suppressed reflex milk ejection in intact, sham-lesioned and control-lesioned rats, but had no effect on either the pattern or magnitude of reflex milk ejection in rats with lesions of the subfornical organ. The subfornical organ, which is situated at the interface between the blood, brain and the cerebrospinal fluid appears to mediate, at least in part, the relaxin-induced inhibition of reflex milk ejection in the rat.

Animals↗