Mechanism of the Haemotensive Action of Porcine Relaxin in Anaesthetized Rats

Abstract

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...

Quantitative autoradiographic studies of relaxin binding in rat atria, uterus and cerebral cortex: characterization and effects of oestrogen treatment

“…Relaxin also has direct e ects on nonreproductive tissues and produces powerful chronotropic and inotropic responses in rat isolated atria (Kakouris et al, 1993), participates in the regulation of blood pressure (Mumford et al, 1989;Parry et al, 1990) and¯uid balance (Weisinger et al, 1993), and releases vasopressin and oxytocin (Dayanithi et al, 1987;Way & Leng, 1992) by activating the neurosecretory magnocellular hypothalamic nuclei (Oshero & Phillips, 1991;McKinley et al, 1997). These e ects may relate to some of the physiological changes observed in females during pregnancy.…”

Relaxin‐induced increased coronary flow through stimulation of nitric oxide production

“…Moreover, RLX has been reported to decrease blood pressure and to blunt the response to vasoconstrictors in mesenteric vasculature in spontaneously hypertensive rats (St-Louis & Massicotte, 1985;Massicotte et al, 1989). RLX has also been found to have positive chronotropic and inotropic effects on the rat heart (Parry et al, 1990;Kakouris et al, 1992;Ward et al, 1992), most likely by binding to high affinity specific receptors in the heart atria (Osheroff et al, 1992;Osheroff & Ho, 1993). More recently, cardiocytes derived from the atria of rats have been shown to secrete detectable amounts of RLX (Taylor & Clark, 1994), which it has been suggested may act via autocrine and/ or paracrine routes to regulate cardiovascular structure and function, thus strengthening the idea that the heart is a physiological target organ for RLX.…”

The Emerging Concept of Relaxn as a Centrally Actng Peptide Hormone with Hemodynamic Actions

“…a number of hemodynamic actions of relaxin have been described (4,5). The balance of the data, however, suggests that relaxin is hypertensive and exerts this effect through an action at the level of the brain (6)(7)(8)(9) and on the heart (10, 11).…”