Browsing by Author "Schneider, Daniela"

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    Administration of angiotensin II and a bradykinin B2 receptor blocker in midpregnancy impairs gestational outcome in guinea pigs
    (2014) Valdés Stromilli, Gloria; Schneider, Daniela; Corthorn H., Jenny; Ortíz, Rita; Acuña, Stephanie; Padilla, Oslando
    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.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.
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    Bradykinin Exerts Independent Effects on Trophoblast Invasion and Blood Pressure in Pregnant Guinea Pigs
    (2020) Valdes, Gloria; Acuna, Stephanie; Schneider, Daniela; Ortiz, Rita; Padilla, Oslando
    Introduction: The pleiotropic kininogen-kallikrein-kinin system is upregulated in pregnancy and localizes in the uteroplacental unit. To identify the systemic and local participation of the bradykinin type 2 receptor (B2R), this was antagonized by Bradyzide (BDZ) during 2 periods: from days 20 to 34 and from days 20 to 60 in pregnant guinea pigs. Methods: Pregnant guinea pigs received subcutaneous infusions of saline or BDZ from gestational day 20 until sacrifice on day 34 (Short B2R Antagonism [SH-B2RA]) or on day 60 (Prolonged B2R Antagonism [PR-B2RA]). In SH-BDZA, systolic blood pressure was determined on day 34, while in PR-BDZA it was measured preconceptionally, at days 40 and 60. On gestational day 60, plasma creatinine, uricemia, proteinuria, fetal, placental and maternal kidney weight, and the extent of trophoblast invasion were evaluated. Results: The SH-B2RA increased systolic blood pressure on day 34 and reduced trophoblast myometrial invasion, spiral artery remodeling, and placental sufficiency. The PR-B2RA suppressed the normal blood pressure fall observed on days 40 and 60; vascular transformation, placental efficiency, urinary protein, serum creatinine, and uric acid did not differ between the groups. The proportion of all studied mothers with lost fetuses was greater under BDZ infusion than in controls. Conclusion: The increased systolic blood pressure and transient reduction in trophoblast invasion and fetal/placental weight in the SH-B2R blockade and the isolated impact on blood pressure in the PR-B2R blockade indicate that bradykinin independently modulates systemic hemodynamics and the uteroplacental unit through cognate vascular and local B2R receptors.
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    INTRAUTERINE GROWTH RESTRICTION IN GUINEA PIG IMPAIRS UMBILICAL AND SYSTEMIC VASCULAR FUNCTION
    (W B SAUNDERS CO LTD, 2015) Herrera, Emilio A.; Schneider, Daniela; Alegria, Rene; Figueroa, Esteban; Villanueva, Cristian; Farias, Marcelo; Casanello, Paola; Krause, Bernardo J.