Inhibitor of complement activation attenuates placental ischemia‐induced hypertension in rat

Abstract

Preeclampsia is characterized by compromised placental perfusion and new onset hypertension during pregnancy. The complement system is part of the innate immune system and complement activation is known to increase in preeclampsia.HypothesisComplement activation is critical for placental ischemia‐induced hypertension. To test the hypothesis, we used the reduced uteroplacental perfusion pressure (RUPP) model of placental ischemia to induce hypertension and determined the effect of inhibiting complement activation using a recombinant soluble form of an endogenous complement regulator, soluble complement receptor‐1 (sCR1; CDX‐1135). On gestation day 14 (term = 21 d) rats underwent sham surgery or clips were placed on the inferior abdominal aorta and ovarian arteries to create RUPP. RUPP and Sham animals received 15 mg/kg sCR1 or saline (Veh) on days 14–18 and mean arterial pressure (MAP) was measured day 19 via arterial catheter. Circulating complement component 3 decreased in RUPP vs Sham (p<0.05) suggesting the component had been cleaved and complement activation had occurred. MAP increased in RUPP‐Veh rats compared to Sham‐Veh rats (109 ± 3 vs 95 ± 3 mmHg), and sCR1 treatment significantly attenuated the increase in MAP in RUPP rats (99 ± 3 mmHg, p<0.05). Thus, inhibition of complement activation may be a viable treatment for hypertension in preeclampsia. Support: Univ Minn Grant‐in‐Aid & NIH HL109843.