Long-term presence of angiotensin II type 1 receptor autoantibody reduces aldosterone production by triggering Ca2+ overload in H295R cells

Preeclamptic women are reported to have inadequate plasma volume expansion coupled with a suppressed secretion of aldosterone; however, the specific mechanism of preeclampsia remains unclear. We demonstrated that the presence of long-term angiotensin II type 1 receptor autoantibody (AT1-AA) reduces aldosterone production by triggering a Ca²⁺ overload in H295R cells. AT1-AA was discovered in preeclamptic women and reported to activate AT₁R, and consequently elevate intracellular Ca²⁺. We found that AT1-AA significantly prolonged the time of intracellular Ca²⁺ elevation. Besides promoting aldosterone production as a second messenger, Ca²⁺ overload shows a cytotoxic effect. Our data reveals that long-term presence of AT1-AA triggered a Ca²⁺ overload and consequent impairment of aldosterone production, which could be prevented by a PKC inhibitor, Gö 6983, or a calcium channel inhibitor, nifedipine. These findings have clinical significance because AT₁R blockers are not recommended for treatment of preeclampsia due to their potential harm to the fetus. Our findings also emphasize a potential clinical benefit of immunoadsorption or neutralization of AT1-AA in preeclamptic women.