AT1R antagonism improves metabolic and vascular changes of obesity-induced gestational diabetes mellitus

Damián A. Madrigal Aguilar, Cecilia Tufiño, Eduardo Fernandez-Martinez, Ismael Bracho-Valdés, Rosa A. Bobadilla Lugo

Research output: Contribution to journalArticlepeer-review


Obesity can overload glucose homeostasis and physiological insulin resistance during gestation which increases the risk of complications like diabetes mellitus or preeclampsia. Angiotensin II /AT1 receptors are involved in the pathogenesis of vascular effects of obesity/insulin resistance but its role during gestation is not as clear. We sought to determine angiotensin II- AT1R participation on a diet-induced gestational diabetes mellitus (GDM) experimental model. Female Wistar rats were fed with a standard or hypercaloric diet for 7 weeks. Half of the animals were mated and became pregnant from week 4–7. Animals were treated with saline, irbesartan (30 mg/kg) or metformin (320 mg/kg) for the last two weeks of the protocol. Weight gain, systolic blood pressure (BP), oral glucose tolerance test and vascular contractility were measured at the last day of the protocol (day 19–20 of pregnancy). Hypercaloric diet increased blood glucose, impaired glucose tolerance test, and increased BP in pregnant rats, fulfilling criteria for GDM. Both drugs decreased impaired GTT and relative hyperglycemia. Metformin had no effect on BP but prevented weight increase. In isolated aortas, irbesartan and metformin decreased vasoconstriction only of non-pregnant hypercaloric diet fed animals. Results support angiotensin II/ AT1R involvement in BP and glucose homeostasis disturbances observed in present GDM model. Also, provide evidence that a hypercaloric diet can mask pregnancy´s physiological hypoglycemia and hypotension without surpassing non-pregnant values. Then, we conclude overweight during pregnancy causes subtle but significant vascular and metabolic damage that might be dismissed in clinical practice.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
Issue number2
StatePublished - Jun 2019


  • Angiotensin II AT1 receptors
  • Gestational diabetes mellitus
  • Irbesartan
  • Metformin

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