Experiments were done to examine the pressor effect of iv porcine relaxin in anaesthetized rats. Acute injections of relaxin caused consistent and sustained rises in systemic blood pressure that were dose-dependent within the physiological range. Pretreatment of rats with a specific vasopressin ( V l ) receptor antagonist, but not an a-adrenoreceptor antagonist, substantially reduced the pressor effect of relaxin. After the vasopressin receptor antagonist, small rises in blood pressure occurred after a longer latent period, compared with the responses in intact animals. The data clearly indicate that acute injections of relaxin cause a pressor response that is predominantly affected via the release of vasopressin. The possible sources of the persistent hypertensive component are discussed and it is suggested that relaxin might act through the central angiotensinergic systems to release vasopressin and cause a pressor response.Plasma relaxin concentrations show marked changes during pregnancy in many species (1). In the rat, the levels of relaxin become detectable from about Day 10 of gestation and rise progressively to reach levels of approximately 100 ng/ml by Day 19. Immediately before birth there is a further, substantial rise in plasma relaxin, followed by a precipitous fall (2). Relaxin has well established roles in the periphery preparing the uterus, cervix and ligaments of the pelvic girdle for birth (1). It also appears to have a central role controlling the release of oxytocin and may be important for determining the timing of birth (3). However, relaxin may also modulate the release of vasopressin, and thereby affect blood pressure. Reports in the literature concerning the effects of relaxin on blood pressure are conflicting and contradictory. Miller et al. (4) first reported that injection of an extract of pregnant sow ovary caused a transient fall in blood pressure when injected into anaesthetized dogs. In contrast, injection of up to 50 pg purified porcine relaxin in anaesthetized rats did not affect blood pressure (5). Preliminary experiments reported by Jones and Summerlee (6) indicated that acute iv injections of a standard dose of relaxin caused a rise in blood pressure and the release of vasopressin. These latter experiments are consistent with the centrally mediated pressor effect of relaxin injected into the third ventricle that is also accompanied by a release of vasopressin (7). The purpose of the present experiments was a thorough reexamination of the possible pressor effects of iv relaxin in anaesthetized rats, to clarify the extent of the pressor response, whether or not it was dose-dependent and to elucidate the possible mechanisms of action. ResultsPressor effects of iv injections of relaxin Acute iv injections of porcine relaxin caused significant (P < 0.01) and sustained increases in blood pressure, compared with control injections of either non-relaxin protein or saline, in anaesthetized female rats (Fig. 1). These increases were dose-dependent within the range 1.25 pg to 10...

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.

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.

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.

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.