Attenuation of antepartum relaxin surge and induction of parturition by antiprogesterone RU 486 in sheep

Gazal, O.S.; Li, Y.; Schwabe, Christian; Anderson, L. L.

doi:10.1530/jrf.0.0970233

Cited by 22 publications

(8 citation statements)

References 33 publications

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“…This corroborates earlier reports, which found relaxin in sheep by using assays directed against porcine relaxin (20,28). These findings are in agreement with the current knowledge from sequencing and phylogenetic analysis; relaxin-2 and -3 are expressed in all mammals, whereas only primates possess relaxin-1 (46).…”

Section: Discussionsupporting

confidence: 93%

Increase of cortical cerebral blood flow and further cerebral microcirculatory effects of Serelaxin in a sheep model

Bischoff

Schmidt

Irintchev

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Serelaxin, recombinant human relaxin-2, modulates endothelial vasodilatory functionality and is under evaluation for treatment of acute heart failure. Little is known about acute effects on cerebral perfusion. We tested the hypothesis that Serelaxin might also have effects on the cerebral microcirculation in a sheep model, which resembles human brain structure quite well. We used laser Doppler flowmetry and sidestream dark-field (SDF) imaging techniques, which are reliable tools to continuously assess dynamic changes in cerebral perfusion. Laser Doppler flowmetry shows that bolus injection of 30 g Serelaxin/kg body wt induces an increase (P ϭ 0.006) to roughly 150% of cortical cerebral blood flow (CBF), whereas subcortical CBF remains unchanged (P ϭ 0.688). The effects on area-dependent CBF were significantly different after the bolus injection (P ϭ 0.042). Effects on cortical CBF were further confirmed by SDF imaging. The bolus injection of Serelaxin increased total vessel density to 127% (P ϭ 0.00046), perfused vessel density to 145% (P ϭ 0.024), and perfused capillary density to 153% (P ϭ 0.024). Western blotting confirmed the expression of relaxin receptors RXFP1 and truncated RXFP2-variants in the respective brain regions, suggesting a possible contribution of RXFP1 on the effects of Serelaxin. In conclusion, the injection of a high dose of Serelaxin exerts quick effects on the cerebral microcirculation. Therefore, Serelaxin might be suitable to improve cortical microcirculation and exert neuroprotective effects in clinically relevant scenarios that involve cortical hypoperfusion. These findings need to be confirmed in relevant experimental settings involving cerebral cortical hypoperfusion and can possibly be translated into clinical practice. RELAXIN-2 IS A HUMAN HORMONE that mediates cardiovascular adaptations during pregnancy and particularly systemic and renal vasodilatation (7). Moreover, these effects are observed in nonpregnant animals and in ex vivo studies following the artificial administration of the substance as well (33). An intravenous bolus injection of a recombinant form of human relaxin-2, Serelaxin (Novartis Pharma, Basel, Switzerland), modulates a sustained endothelial vasodilatory function. Serelaxin mediates systemic hemodynamic changes and increases renal blood flow through a fall in systemic intravascular resistance with a concomitant increase in arterial compliance (15,22,31,38,39). In the RELAX-AHF study, cardiovascular and all-cause mortality was reduced 37% in patients treated with Serelaxin (42). Furthermore, initial positive studies on the cerebral effects of this peptide hormone in a stroke model (47) and in a high blood pressure situation (6) have already been published. Serelaxin induces a nitric oxide-mediated vasodilatation (40) and can particularly reduce the infarction size of the cerebral cortex, suggesting a neuroprotective effect (47).Nonetheless, studies on the influence of Serelaxin on the cerebral blood flow (CBF) have not been performed to this day. Moreover, desp...

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Section: Discussionsupporting

confidence: 93%

Increase of cortical cerebral blood flow and further cerebral microcirculatory effects of Serelaxin in a sheep model

Bischoff

Schmidt

Irintchev

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…IP also provides well-timed manipulation of the newborn lambs and the ewes during parturition (24,33,34,40). Many hormones and medications are used for IP in ewes, including adrenocorticotropic hormone (ACTH) (8), glucocorticoids, PGF 2α and analogues, 3β-hydroxysteroid dehydrogenase enzyme inhibitors (epostane and trilostane) (24,33), progesterone receptor blockers (21,29), and synthetic PGE 1 analogues (misoprostol) (36). Glucocorticoid usage is a well-known conventional choice to terminate gestation in the veterinary field (1,5,26).…”

Section: Introductionmentioning

confidence: 99%

“…Glucocorticoid usage is a well-known conventional choice to terminate gestation in the veterinary field (1,5,26). Because progesterone plays a primary role in continuing gestation, the application of antiprogestine drugs (mifepristone or aglepristone) has been popular in recent studies (3,12,19,21).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the endocrinological and immunological results of different induction of parturition methods in ewes

Salci¹,

Demirbilek²,

Güneş³

et al. 2018

Tierarztl Prax Ausg G

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SummaryObjective: This study aimed to compare different induction of parturition (IP) methods in terms of endocrinological and immunological parameters in ewes and lambs. Materials and methods: A total of 24 ewes and their respective 24 lambs were studied. Groups of six ewes were induced on the 138th day: groups I (control), II (dexamethasone), III (aglepristone) and IV (aglepristone + dexamethasone). Blood samples were taken from the ewes from IP to 2 days postpartum at 12-hour intervals for the prolactin and oxytocin analyses. Colostrum and blood samples were collected from the lambs at 0, 12, 24, 36 and 48 hours for the IgG analysis. The prolactin, oxytocin and IgG levels were measured by ELISA. Results: A significant difference was found in prolactin levels in all groups and in the colostral IgG level in group IV with respect to the sampling time. Additionally, a significant difference in prolactin level was found at 24 hours postpartum between group IV and groups I and III. A significant difference in the colostral IgG level was determined at 24 hours after parturition between group III and the other groups and at 48 hours after parturition between groups II and III. A positive and significant correlation between the colostral and serum IgG levels of the lambs was found at 24 hours in groups I and II. Conclusion and clinical relevance: Although varying individual results were found within the groups, the endocrinological and immunological results did not suggest any superiority among the IP methods. Considering the presented study results, a single dose of aglepristone may be used alone or in combination with dexamethasone for IP.

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“…1993). In small ruminants, mifepristone has been also used to induce parturition (Gazal et al. 1993) in ewes.…”

Section: Introductionmentioning

confidence: 99%

“…However, other studies were inconsistently successful in inducing parturition after the administration of mifepristone in bitches (Nohr et al 1993). In small ruminants, mifepristone has been also used to induce parturition (Gazal et al 1993) in ewes.…”

Section: Introductionmentioning

confidence: 99%

Induction of Parturition with Aglepristone in the Majorera Goat

Batista

Reyes

Santana

et al. 2011

Reprod Domestic Animals

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This study assessed the efficacy of aglepristone at inducing parturition in pregnant goats. Six experimental groups were defined: group A-5 (n = 12), group A-3.3 (n = 12), group A-2.5 (n = 12) and group A-1.5 (n = 12) in which goats were injected SC once with 5.0, 3.3, 2.5 and 1.5 mg of aglepristone per kg body weight of goat, respectively, group L (n = 11), which was treated IM with 3.75 mg of luprostiol; and group Ct (n = 11), which was injected SC with 1 ml of saline solution. Different parameters associated with parturition were thereafter investigated. In addition, plasma progesterone concentrations were defined after treatments till parturition. Aglepristone effectively induced parturition in all of the goats. In the A-5, A-3.3 and A-2.5 groups, the time to parturition was around 30-34 h, and the majority of goats (97.2%, 35/36) started kidding between 25 and 40 h after the aglepristone injection. However, the goats in group A-1.5 showed a significantly (p < 0.01) higher time to parturition (mean: 46.8 h). Overall, the incidence of dystocia registered in aglepristone-induced goats (20.8%, 10/48) and luprostiol-induced goats was not different from that observed after a spontaneous parturition. The percentage of live kids was very similar between A-5, A-3.3, A.2.5 and L groups (95.7, 95.3, 95.0 and 96.3%, respectively) but was higher that observed in the control (83.4%) and A-1.5 (81.2%) groups. In addition, no maternal mortality was registered in any groups. No changes in plasma progesterone were observed during the first 24 h after treatment, and high plasma progesterone concentrations were present at kidding (6.7, 5.5, 4.5 and 3.6 ng/ml for groups A-5, A-3.3, A-2.5 and A-1.5, respectively), confirming that aglepristone does not induce parturition via luteolysis. This study demonstrates that aglepristone can be used to induce parturition in goats with satisfactory efficacy, inducing pregnancy termination without direct or immediate modifications of luteal function.

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Attenuation of antepartum relaxin surge and induction of parturition by antiprogesterone RU 486 in sheep

Cited by 22 publications

References 33 publications

Increase of cortical cerebral blood flow and further cerebral microcirculatory effects of Serelaxin in a sheep model

Increase of cortical cerebral blood flow and further cerebral microcirculatory effects of Serelaxin in a sheep model

Comparison of the endocrinological and immunological results of different induction of parturition methods in ewes

Induction of Parturition with Aglepristone in the Majorera Goat

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