Abstract P257: Investigating Angiotensin II Infusion as a Model of Superimposed Preeclampsia in Pregnant Stroke Prone Spontaneously Hypertensive Rats

Abstract

Background: Hypertensive disorders of pregnancy are a leading cause of maternal mortality worldwide. Chronic hypertension with superimposed preeclampsia is becoming more prevalent in modern society. Animal models are vital for understanding this condition. Our aim was to induce a preeclamptic phenotype in pregnant stroke prone spontaneously hypertensive (SHRSP) rats by angiotensin II (AngII) infusion. Methods: AngII, at a dose of 500ng/kg/min or 1000ng/kg/min, was administered by minipump in pregnant SHRSP rats from gestational day (GD)10. Cardiovascular and renal changes were monitored using radiotelemetry, echocardiography and weekly urine collections. GD18 ex vivo uterine artery function and structure were assessed using myography. Results: Both AngII doses resulted in an immediate and sustained increase in systolic blood pressure compared to vehicle control ( 172.5±5.0mmHg; 500ng/kg/min and 204.1±5.6mmHg; 1000ng/kg/min vs 159.0±0.4mmHg; p<0.001 ). Cardiac output increased over pregnancy in the vehicle group ( 53±6L/min vs 81±5L/min; p<0.01 ), however this trend was not observed in 500ng/kg/min treatment group ( 60±6L/min vs 56±11L/min ) and was reversed in 1000ng/kg/min treatment group ( 60±6L/min vs 36±6L/min; p<0.01 ). GD14 urinary albumin:creatinine ratios were significantly increased in both treatment groups ( 1.3±0.2; 500ng/kg/min, 2.9±0.1; 1000ng/kg/min vs 0.5±0.2; vehicle; p<0.05, p<0.001 ). Uterine arteries in the 1000ng/kg/min treatment group demonstrated significantly reduced cross-sectional area ( 4.8x10 4 ±32μm 2 vs 7.6x10 4 ±16μm 2 ; p<0.01 ). Both treatment groups had a reduced vasorelaxation to 2x10 5 M carbachol ( 93.6±3.9%; 500ng/kg/min, 84.7±4.3%; 1000ng/kg/min vs 56.9±21.1%; vehicle; p<0.05 ) and contractile response to 2x10 5 M noradrenaline demonstrated an increased trend in both treatment groups ( 66.9±16.1KPa; 500ng/kg/min, 61.8±6.2KPa; 1000ng/kg/min vs 45.1±5.7KPa; vehicle ). Conclusion: This study demonstrates that AngII infusion in pregnant SHRSP rats can mimic specific haemodynamic, cardiac and urinary profiles common to preeclamptic women. This rodent model of superimposed preeclampsia will be crucial for detailed investigation of underlying causes and treatment options for this condition.