Baeza-Pérez Lourdes Graciela, Cabrera-Becerra Sandra Edith, Romero-Nava Rodrigo, Ramos-Tovar Erika, Hernández-Campos Maria Elena, López-Sánchez Pedro
Laboratorio de Farmacología Molecular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Sto. Tomás, Ciudad de México, México.
These authors contributed eqully to this work.
Iran J Basic Med Sci. 2024;27(5):621-629. doi: 10.22038/IJBMS.2024.72486.15790.
Preeclampsia (PE) is a complication of pregnancy that might increase progeny risk of cardiovascular and metabolic problems, mainly in males. Renin angiotensin aldosterone system is known to be involved. (Pro) renin/renin receptor ((P)RR) has been shown to participate in cardiovascular pathology. The aim of this work was to evaluate (P)RR expression and function upon cardiovascular and renal tissues from PE dams' offspring.
We used offspring from normal pregnant and preeclamptic rats, evaluating body, heart, aorta and kidney weight, length, and blood pressure along 3 months after birth. Subsets of animals received handle region peptide (HRP) (0.2 mg/Kg, sc). Another group received vehicle. Animals were sacrificed at first, second, and third months of age, tissues were extracted and processed for immunoblot to detect (P)RR, PLZF, β-catenin, DVL-1, and PKCα. (P)RR and PLZF were also measured by RT-PCR.
We found that offspring developed hypertension. Male descendants remained hypertensive throughout the whole experiment. Female animals tended to recover at second month and returned to normal blood pressure at third month. HRP treatment diminished hypertension in both male and female animals. Morphological evaluations showed changes in heart, aorta, and kidney weight, and HRP reverted this effect. Finally, we found that (P)RR, PLZF, and canonical WNT transduction pathway molecules were stimulated by PE, and HRP treatment abolished this increase.
These findings suggest that PE can induce hypertension in offspring, and (P)RR seems to play an important role through the canonical WNT pathway and that gender seems to influence this response.
子痫前期(PE)是一种妊娠并发症,可能会增加后代患心血管和代谢问题的风险,主要是男性。已知肾素血管紧张素醛固酮系统参与其中。(前体)肾素/肾素受体((P)RR)已被证明参与心血管病理过程。这项工作的目的是评估PE母鼠后代的心血管和肾脏组织中(P)RR的表达及功能。
我们使用正常妊娠和子痫前期大鼠的后代,在出生后3个月内评估其体重、心脏、主动脉和肾脏的重量、长度以及血压。部分动物接受柄区肽(HRP)(0.2mg/Kg,皮下注射)。另一组接受赋形剂。在动物1月龄、2月龄和3月龄时处死,提取组织并进行免疫印迹分析,以检测(P)RR、PLZF、β-连环蛋白、DVL-1和PKCα。(P)RR和PLZF也通过RT-PCR进行检测。
我们发现后代出现了高血压。雄性后代在整个实验过程中一直保持高血压状态。雌性动物在2月龄时趋于恢复,3月龄时血压恢复正常。HRP治疗降低了雄性和雌性动物的高血压。形态学评估显示心脏、主动脉和肾脏重量发生了变化,HRP逆转了这种影响。最后,我们发现PE刺激了(P)RR、PLZF和经典WNT转导通路分子,而HRP治疗消除了这种增加。
这些发现表明,PE可诱导后代高血压,(P)RR似乎通过经典WNT途径发挥重要作用,而且性别似乎会影响这种反应。