Abstract
Preeclampsia is a pregnancy-specific condition manifested by new-onset maternal hypertension with systemic inflammation, including increased innate immune system complement activation. While exact pathophysiology is unknown, evidence suggests that inadequate spiral artery invasion and resulting utero-placental insufficiency is the initiating event. Cigarette smoking during pregnancy decreases the risk of preeclampsia. Nicotine, a major component of cigarettes, stimulates the efferent cholinergic anti-inflammatory pathway through peripherally expressed nicotinic acetylcholine receptors (nAChR) and is known to attenuate ischemia–reperfusion injury in kidney and liver. Prior studies indicated that complement activation was critical for placental ischemia-induced hypertension in a rat model. Thus, it was hypothesized here that nicotine was responsible for the protective effect of cigarette smoking in preeclampsia and would attenuate placental ischemia-induced systemic complement activation and hypertension. The Reduced Utero-placental Perfusion Pressure (RUPP) model in the pregnant rat was employed to induce placental ischemia, resulting in complement activation, fetal resorptions, and hypertension. On gestation day (GD)14, nicotine (1 mg/kg) or saline was administered via subcutaneous injection prior to RUPP surgery and daily through GD18. On GD19, placental ischemia significantly increased mean arterial pressure (MAP) in saline injected animals. However, the placental ischemia-induced increase in blood pressure was not evident in nicotine-treated animals and nicotine treatment significantly increased MAP variability. Circulating C3a was measured as an indicator of complement activation and increased C3a in RUPP compared to Sham persisted with nicotine treatment, as did fetal resorptions. These data suggested to us that nicotine may contribute to the decreased risk of preeclampsia with cigarette smoking, but this protective effect was confounded by additional effects of nicotine on the cardiovascular system.
Highlights
Hypertensive disorders in pregnancy affect ≈ 10% of pregnancies (Abaolos et al 2013)
Previous studies in the reduced uteroplacental perfusion pressure (RUPP) model indicate that placental ischemia modestly attenuates acetylcholine-induced relaxation of mesenteric arteries (Lillegard et al 2014)
Complement activation and systemic inflammation are implicated in preeclampsia and we previously demonstrated that complement inhibition in the RUPP model attenuates associated hypertension, suggesting inhibition of complement activation may be a viable therapeutic strategy (Lillegard et al 2013)
Summary
Hypertensive disorders in pregnancy affect ≈ 10% of pregnancies (Abaolos et al 2013). As a subset of such pregnancy-specific disorders, preeclampsia is the leading cause of maternal and perinatal mortality and morbidity worldwide, affecting up to 4% of pregnancies (Ananth et al 2013). Preeclampsia is characterized by new-onset maternal hypertension and proteinuria, though recent ACOG criteria recognize preeclampsia in the absence of proteinuria if systemic symptoms include thrombocytopenia, impaired liver, development of renal insuffi-ciency, pulmonary edema, or cerebral or visual disturbances (ACOG 2013; Ananth et al 2013). The precise mechanisms involved are incompletely understood, the predominant theory posits the initiating event of inadequate spiral artery invasion limiting utero-placental blood flow, reducing placental perfusion in the first half of pregnancy and resulting in symptoms of preeclampsia during the second half of pregnancy (Fisher 2015).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
