Pyridostigmine ameliorates preeclamptic features in pregnant rats by inhibiting tumour necrosis factor-α synthetsis and antagonizing tumour necrosis factor-α-related effects

Objective:Preeclampsia is a hypertensive disorder of pregnancy marked by an excessive inflammatory response. The anti-inflammatory effect of pyridostigmine (PYR) was previously reported; however, its role in hypertensive pregnancies remains unclear. We hypothesized that PYR could attenuate increased blood pressure and other pathological features in preeclampsia models.Methods:The expression of tumour necrosis factor (TNF)-α was evaluated in normal and preeclampsia pregnant women. PYR (20 mg/kg) was administered daily to reduced uterine perfusion pressure (RUPP) and TNF-α (150 ng/day) infused rats from gestation day 14 to GD19. In a cell culture experiment, the effect of acetylcholine (ACh) on TNF-α-stimulated primary human umbilical endothelial cells (HUVEC) was assessed.Results:Preeclampsia women had higher placental TNF-α expression than normal pregnant women. Mean arterial pressure (MAP) in the RUPP group was higher than in the Sham group. PYR inhibited serum and placental acetylcholinesterase activity in rats, and reduced MAP, placental oxidative stress, apoptosis and inflammation in the RUPP group but not in the Sham group. In addition, PYR significantly attenuated the TNF-α-induced increase in MAP, placental oxidative stress and apoptosis. Moreover, TNF-α decreased cell viability and increased the number of TUNEL-positive nuclei of HUVEC, which could largely be abolished by ACh treatment.Conclusion:Collectively, PYR ameliorated hypertension and other preeclampsia-like symptoms in rat models of preeclampsia not only by inhibiting the synthesis of TNF-α but also by acting against TNF-α-induced detrimental effects directly, which is worthy of further investigation and may be used as a potential agent for preeclampsia management.