Cardiovascular Programming by Preeclampsia Sensitizes Mother Rats to Hemodynamic and Cardiac Autonomic Depressant Effects of Postpartum Endotoxemia

Abstract

Preeclampsia is a pregnancy related disorder with serious maternal and fetal consequences. Considering that postpartum infection and endotoxemia are important causes of maternal death, we investigated whether preeclamptic maternal programming alters cardiovascular and cardiac autonomic consequences of endotoxemia in rats. Preeclampsia was induced by daily oral administration of 50 mg/kg of L‐NAME for 7 days starting from day 14 of conception. Changes in blood pressure (BP), heart rate (HR), and cardiac sympathovagal balance caused by i.v. administration of lipopolysaccharide (LPS) were assessed in conscious mothers pre‐instrumented with femoral indwelling catheters at 3 weeks (weaning time) and 9 weeks postpartum. At weaning, LPS caused significantly greater falls in BP and rises in HR and LV contractility (dP/dtmax) in PE rats compared with their non‐PE counterparts. Additionally, more apparent reductions in time and frequency domain indices of heart rate variability and shifts in cardiac sympathovagal balance (low‐frequency/high‐frequency ratio, LF/HF) towards parasympathetic dominance were observed after treatment of weaning PE mothers with LPS. Measurement of arterial baroreflex activity by the vasoactive method revealed that LPS attenuated reflex bradycardic responses to phenylephrine in endotoxic PE, but not non‐PE, weaning rats. Remarkably, the intensified cardiovascular effects of endotoxemia in weaning PE rats were found to subside after 9 weeks of delivery. In conclusion, maternal programming by preeclampsia elicits short‐term exacerbation of cardiovascular and autonomic derangements caused by endotoxemia in rats.Support or Funding InformationSupported by the Science and Technology Development Fund, Egypt (STDF Grants No. 14895)