The GLP‐1 agonist liraglutide lowers blood pressure in a placental ischemic model of preeclampsia
Authors: Younes Subhi Talal , Ryan Michael 
Published: June 2021

Preeclampsia is a multi‐system disorder of pregnancy characterized by widespread vascular dysfunction. Though the precise etiology of preeclampsia remains largely enigmatic, emerging evidence suggests that an ischemic placenta releases circulating vasoactive factors all of which culminate in endothelial dysfunction. The incretin hormone glucagon‐like peptide 1 (GLP‐1) has been extensively studied for its therapeutic benefit in diabetes mellitus, where it acts to enhance endogenous insulin secretion. In addition to its role in glucose homeostasis, GLP‐1 receptors are present on endothelial cells and activate the endothelial nitric oxide synthase (eNOS) signaling axis. In turn, GLP‐1 receptor agonists have been demonstrated to improve endothelial dysfunction. Therefore, we hypothesized that administration of a GLP‐1 receptor agonist would attenuate endothelial dysfunction and improve blood pressure in our model of preeclampsia.

In order to test this hypothesis, timed pregnant CD‐001 rats (an outbred sub‐strain of Sprague‐Dawley rats) underwent surgery on gestation day 15 to place silver clips on the aorta and ovarian‐uterine arterial anastomoses. This procedure restricts blood flow to the fetal‐placental unit by 60%, producing a model of reduced uterine perfusion pressure (RUPP) that mimics several characteristics of human preeclampsia. From gestation day 15 to 20, animals received daily subcutaneous injections of 0.3 mg/kg liraglutide or vehicle. Animals were instrumented with carotid catheters on gestation day 19 and blood pressure determined on day 20 while the animals were conscious and restrained. Daily weight, food intake, and pup outcome were collected.

We found that blood pressure was significantly lower in RUPP animals treated with liraglutide (107.8 ±2.5 vs 117.6 ±4.0 mmHg, n = 5 and 8 respectively, p<0.05). Though food intake was diminished in the liraglutide‐treated group immediately following surgery (2.0 ±0.6 vs. 10.8 ±1.6 grams/day on gestation day 15), it rapidly recovered (16.3 ±1.6 vs. 14.5 ±1.8 grams/day on gestation day 19), and there was no significant difference between body weight (259±10 vs 287 ±14 grams on gestation day 20), litter size (8 ±2 vs 10 ±1 live pups), or pup weight (2.07 ±0.05 vs 2.15 ±0.11 grams).

This data shows that GLP‐1 receptor agonism effectively lowers blood pressure in a placental ischemic model of preeclampsia. Although the mechanisms contributing to the improved blood pressure remain unclear, these data suggest that the GLP‐1 system represents a new potential therapeutic target in preeclampsia. Importantly, given its role in diabetes, several GLP‐1 receptor agonists are already FDA approved. Future studies will examine vascular mechanisms by which GLP‐1 receptor agonism protects against the development of placental ischemia‐induced hypertension.

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18PRE34050024HL136684P20GM104357

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.