Obesity is associated with significant complications during pregnancy, including hypertensive disorders of pregnancy, and increased risk of cardiovascular and renal disease later in life. Surprisingly, we know little about the impact of obesity on the cardiovascular and renal adaptations that occur during a normal pregnancy. The aim of present study was to determine the adaptations that occur in mean arterial pressure (MAP), heart rate (HR) and renal function across pregnancy in a mouse model of diet-induced obesity.
At 4wks of age, female C57BL6J mice were place on a control (Cont; 16% fat, 3.85 kCal/g; n=8) or high fat (HF; 43% fat, 4.54 kCal/g; n=7) diet for 10 weeks and glucose tolerance tests (GTT) performed. Baseline MAP and HR (radio-telemetry), and 24hr urinary albumin excretion (n=3-5/gp) were measured. Mice were then mated, and MAP and HR measured throughout gestation with 24hr albumin excretion reassessed at gestational day (GA) 13.
After 10 wks of the diet, body weight of HF mice was 40% greater than Cont mice (33.2±1.8 vs 23.6±0.6g; P<0.001). Both groups of mice had similar fasting blood glucose. The obese mice were, however, glucose intolerant compared to Cont mice (725±60 vs 467±64, Area Under the Curve; P<0.05), had elevated basal MAP (105.2±2.1 vs 99.3±1.6mmHg; P<0.05), HR (556±13 vs 492±17bpm; P<0.05) and were albuminuric (4.53±0.62 vs 2.42±0.42μg/24h; P<0.05). Following mating, MAP (Pdiet<0.01) and HR (Pdiet<0.05) of obese mice remained elevated over Cont mice throughout pregnancy. However the adaptations of MAP and HR in obese mice over pregnancy, including the dip in MAP at GA9, were consistent in timing and magnitude with Cont mice. Pregnancy led to a significant increase in 24hr albumin excretion at GA13 (Ppreg<0.001), however this effect was exacerbated in obese mice (9.95±0.88 vs 4.03±1.1μg/24h; PpregXdiet <0.01).
Obesity results in higher MAP and HR before pregnancy and both remain elevated throughout pregnancy without altering the normal adaptations of MAP and HR during pregnancy. Importantly, pregnancy exacerbates albuminuria in obese females suggesting that obese pregnancy might increase the risk of renal complications during pregnancy and lead to renal disease in the long-term.