882: A role for natural killer cells in the pathophysiology of preeclampsia

Abstract

Pregnant rats were dived into normal pregnant (NP) and RUPP groups; RUPP was performed on gestational day (GD) 14, and on GD19 conscious mean arterial blood pressure (MAP) was measured, placentas were collected and mitochondria were isolated. Mitochondrial Electron Transport Chain (ETC) complex I and IV activities were measured spectrophotometrically. Additionally, glutamate/malate was used as complex I substrate to measure respiration. Respiration rates measured included: basal state (no substrates), state 2 (glutamate/malate), state 3 (ADP), state 4 (oligomycin), and maximal state (FCCP). RESULTS: MAP was elevated in RUPP (n¼16) compared to NP rats (n¼14) (119AE2 vs. 100AE2 mmHg, p<0.05). Complex I mediated state 3 and maximal state respiration rates were significantly reduced in RUPP vs. NP (313AE16, n¼7 vs. 423AE15, n¼8, pmol/sec/mg, p<0.01) and (244AE13, n¼7 vs. 300AE11, n¼8, pmol/sec/mg, p<0.01) respectively. Respiratory control ratio (state3/state4) was significantly reduced in RUPP (n¼6) vs. NP rats (n¼8) (7AE1 vs 10AE1, p<0.05). Additionally, ETC complex I (12AE3, n¼3 vs. 23AE2, n¼5 nmol e-/min/mg, P<0.05) and complex IV (509AE14, n¼4 vs. 644AE17, n¼6 nmol e-/min/mg, P<0.01) activities were drastically reduced in RUPP compared to NP rats. CONCLUSION: Impairment of mitochondrial respiration and ETC activities indicate that mitochondrial dysfunction is associated with placental ischemia of pregnancy and thereby could contribute to oxidative stress, hypertension and other pathophysiological features of PE.