Preeclampsia is the most frequent pregnancy-related complication worldwide with no cure. While a number of molecular features have emerged， the underlying causal mechanisms behind the disorder remain obscure. Here， we find that increased complex formation between angiotensin II AT1 and bradykinin B2， two G protein-coupled receptors with opposing effects on blood vessel constriction， triggers symptoms of preeclampsia in pregnant mice. Aberrant heteromerization of AT1-B2 led to exaggerated calcium signaling and high vascular smooth muscle mechanosensitivity， which could explain the onset of preeclampsia symptoms at late-stage pregnancy as mechanical forces increase with fetal mass. AT1-B2 receptor aggregation was inhibited by beta-arrestin-mediated downregulation. Importantly， symptoms of preeclampsia were prevented by transgenic ARRB1 expression or a small-molecule drug. Because AT1-B2 heteromerization was found to occur in human placental biopsies from pregnancies complicated by preeclampsia， specifically targeting AT1-B2 heteromerization and its downstream consequences represents a promising therapeutic approach.