Administration of angiotensin II and a bradykinin B2 receptor blocker in midpregnancy impairs gestational outcome in guinea pigs

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dc.contributor.authorValdés Stromilli, Gloria
dc.contributor.authorSchneider, Daniela
dc.contributor.authorCorthorn H., Jenny
dc.contributor.authorOrtíz, Rita
dc.contributor.authorAcuña, Stephanie
dc.contributor.authorPadilla, Oslando
dc.date.accessioned2019-10-17T13:46:09Z
dc.date.available2019-10-17T13:46:09Z
dc.date.issued2014
dc.date.updated2019-10-14T18:46:48Z
dc.description.abstractAbstract Background The opposing renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) are upregulated in pregnancy and localize in the utero-placental unit. To test their participation as counter-regulators, circulating angiotensin II (AII) was exogenously elevated and the bradykinin B2 receptor (B2R) was antagonized in pregnant guinea-pigs. We hypothesized that disrupting the RAS/KKS balance during the period of maximal trophoblast invasion and placental development would provoke increased blood pressure, defective trophoblast invasion and a preeclampsia-like syndrome. Methods Pregnant guinea-pigs received subcutaneous infusions of AII (200 μg/kg/day), the B2R antagonist Bradyzide (BDZ; 62.5 microg/kg/day), or both (AII + BDZ) from gestational day 20 to 34. Non-pregnant cycling animals were included in a control group (C NP) or received AII + BDZ (AII + BDZ NP) during 14 days. Systolic blood pressure was determined during cycle in C NP, and on the last day of infusion, and 6 and 26 days thereafter in the remaining groups. Twenty six days after the infusions blood and urine were extracted, fetuses, placentas and kidneys were weighed, and trophoblast invasion of spiral arteries was defined in the utero-placental units by immunocytochemistry. Results Systolic blood pressure transiently rose in a subgroup of the pregnant females while receiving AII + BDZ infusion, but not in AII + BDZ NP. Plasma creatinine was higher in AII- and BDZ-treated dams, but no proteinuria or hyperuricemia were observed. Kidney weight increased in AII + BDZ-treated pregnant and non-pregnant females. Aborted and dead fetuses were increased in dams that received AII and AII + BDZ. The fetal/placental weight ratio was reduced in litters of AII + BDZ-treated mothers. All groups that received interventions during pregnancy showed reduced replacement of endothelial cells by extravillous trophoblasts in lateral and myometrial spiral arteries. Conclusions The acute effects on fetal viability, and the persistently impaired renal/placental sufficiency and incomplete arterial remodeling implicate the RAS and KKS in the adaptations in pregnancy. The results partially confirm our hypothesis, as a preeclampsia-like syndrome was not induced. We demonstrate the feasibility of characterizing systemic and local modifications in pregnant guinea-pig, supporting its use to study normal placentation and related disorders.Abstract Background The opposing renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) are upregulated in pregnancy and localize in the utero-placental unit. To test their participation as counter-regulators, circulating angiotensin II (AII) was exogenously elevated and the bradykinin B2 receptor (B2R) was antagonized in pregnant guinea-pigs. We hypothesized that disrupting the RAS/KKS balance during the period of maximal trophoblast invasion and placental development would provoke increased blood pressure, defective trophoblast invasion and a preeclampsia-like syndrome. Methods Pregnant guinea-pigs received subcutaneous infusions of AII (200 μg/kg/day), the B2R antagonist Bradyzide (BDZ; 62.5 microg/kg/day), or both (AII + BDZ) from gestational day 20 to 34. Non-pregnant cycling animals were included in a control group (C NP) or received AII + BDZ (AII + BDZ NP) during 14 days. Systolic blood pressure was determined during cycle in C NP, and on the last day of infusion, and 6 and 26 days thereafter in the remaining groups. Twenty six days after the infusions blood and urine were extracted, fetuses, placentas and kidneys were weighed, and trophoblast invasion of spiral arteries was defined in the utero-placental units by immunocytochemistry. Results Systolic blood pressure transiently rose in a subgroup of the pregnant females while receiving AII + BDZ infusion, but not in AII + BDZ NP. Plasma creatinine was higher in AII- and BDZ-treated dams, but no proteinuria or hyperuricemia were observed. Kidney weight increased in AII + BDZ-treated pregnant and non-pregnant females. Aborted and dead fetuses were increased in dams that received AII and AII + BDZ. The fetal/placental weight ratio was reduced in litters of AII + BDZ-treated mothers. All groups that received interventions during pregnancy showed reduced replacement of endothelial cells by extravillous trophoblasts in lateral and myometrial spiral arteries. Conclusions The acute effects on fetal viability, and the persistently impaired renal/placental sufficiency and incomplete arterial remodeling implicate the RAS and KKS in the adaptations in pregnancy. The results partially confirm our hypothesis, as a preeclampsia-like syndrome was not induced. We demonstrate the feasibility of characterizing systemic and local modifications in pregnant guinea-pig, supporting its use to study normal placentation and related disorders.
dc.fuente.origenBiomed Central
dc.identifier.citationReproductive Biology and Endocrinology. 2014 Jun 04;12(1):49
dc.identifier.doi10.1186/1477-7827-12-49
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/26649
dc.identifier.urihttps://doi.org/10.1186/1477-7827-12-49
dc.issue.numeroNo. 49
dc.language.isoen
dc.pagina.final8
dc.pagina.inicio1
dc.revistaReproductive Biology and Endocrinologyes_ES
dc.rightsacceso abierto
dc.rights.holderValdés et al.; licensee BioMed Central Ltd.
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.otherSistema renina-angiotensinaes_ES
dc.subject.otherCreatininaes_ES
dc.subject.otherGestaciones_ES
dc.titleAdministration of angiotensin II and a bradykinin B2 receptor blocker in midpregnancy impairs gestational outcome in guinea pigses_ES
dc.typeartículo
dc.volumenVol. 12
sipa.codpersvinculados103037
sipa.codpersvinculados102180
sipa.codpersvinculados102063
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