Metformin Mitigates Hemodynamic, Autonomic, Oxidative, and Inflammatory Dysregulation in L-NAME-Induced Preeclampsia

Cardiovascular complications in preeclampsia are challenging and have been known to increase fetal and maternal morbidity and mortality. The objective of this study is to determine how metformin affects BP, HR, ECG, oxidative stress, and inflammatory markers in a preeclampsia-like rat model induced by L-NAME in female albino Wistar rats.

Pregnant rats were randomly divided into four experimental groups: Group I (PC) the pregnant control, received normal saline: Group II (PEC) was treated intraperitoneally with 125 mg/kg/day of L-NAME from GD 13 -21: Group III (MetC) received 400 mg/kg/day Metformin orally from GD 13-GD21; and Group IV(T) was treated with L-NAME (125 mg/kg/day) and Met (400mg/kg/day) from "GD 13- 21". "ECG, hemodynamic, sand Baroreflex Sensitivity (BRS)" values were monitored at Gestational Day 21. Furthermore, cardiac tissue homogenates were evaluated for oxidative stress markers (MDA, GSH, and SOD) as well as inflammatory cytokines (TNF-α and IL-6).

The results showed that the Preeclampsia-like rat model significantly altered the ECG, resulting in increased duration of QRS and TpTe intervals and prolonged RR and QTc intervals. Metformin prevented these changes in rats. In addition, L-NAME decreased heart rate and increased systolic, diastolic, and mean arterial pressures; these effects were reversed by metformin. Elevated MDA indicated oxidative stress in cardiac tissue homogenates. These alterations were largely reversed by metformin, indicating that it had anti-inflammatory and antioxidant effects.

A preeclampsia-like rat model was induced using L-NAME in rats during pregnancy, resulting in hypertension, ECG abnormalities, oxidative stress, and inflammation. Metformin possesses strong cardioprotective, antioxidant, and anti-inflammatory effects, normalizing blood pressure and ECG intervals, reducing urinary protein levels, decreasing MDA levels, and increasing GSH and SOD contents, while also inhibiting the release of TNF-α and IL-6.

In this study, we observed that metformin attenuated hypertension, ECG changes, oxidative stress, and inflammation in a preeclampsia-like rat model. Moreover, metformin enhanced baroreflex sensitivity, leading to partial recovery of autonomic cardiovascular regulation along with improved glycemic control. These results indicate that metformin could be a potential therapeutic intervention for the cardiovascular consequences of preeclampsia.