Abstract P208: Cardiovascular Effects Of Antihypertensive Agents In A Rat Model Of Preeclampsia.

Abstract

Introduction: Hypertensive disorders of pregnancy are a leading cause of maternal and neonatal morbidity and mortality. The placental origin of preeclampsia, characterized by hypertension and proteinuria after 20 weeks of gestation, is currently on the test bench. A number of studies reported a cardiovascular origin for preeclampsia, with increased long-term cardiovascular risk for affected women. Despite new insights into pathophysiology, there is a lack of evidence supporting improvement in maternal and neonatal outcomes with current antihypertensive therapy. This study aims to investigate maternal hemodynamics and cardiovascular parameters in a preeclamptic rat model, focusing on changes induced by antihypertensive treatment. Purpose: This study challenges blood pressure as the sole target for antihypertensive therapy in preeclampsia, seeking new insights into the disease's pathophysiology through invasive procedures and assessment of cardiac morphology in a rat model for preeclampsia. Methods: Maternal hemodynamics were invasively measured, and cardiac compliance was assessed via echocardiography. Cardiac phenotyping was performed combining the evaluation of physiology and structural changes. Maternal hearts were investigated at the end of pregnancy and postpartum. Blood pressure was continuously monitored using telemetry. The antihypertensive agents used in the study were methyldopa, nifedipine, and labetalol, which represent standard therapy for women with preeclampsia. Results: In the transgenic rat model for preeclampsia (PE), treatment with methyldopa and nifedipine led to a reduction of blood pressure during gestation whereas labetalol had no effect on the blood pressure (mean arterial pressure: PE 160.80±3.85 mmHg; PE+methyldopa 145.01±3.71 mmHg; PE+nifedipine 122.08±5.62 mmHg; PE+labetalol 163.12±3.12 mmHg). Despite the antihypertensive effects of methyldopa and nifedipine, the maternal hemodynamics as well as the cardiac compliance were unimproved during and after pregnancy. Conclusion: The results showed that standard therapy for women with preeclampsia does not seem to be sufficient to prevent the cardiovascular changes and therefore to reduce the CDV risk.