Obesity is associated with 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 normal cardiovascular and renal adaptations that occur during pregnancy. We therefore measured mean arterial pressure (MAP), heart rate (HR) and renal function across pregnancy in a mouse model of diet-induced obesity.
Four-week old female C57BL6J mice were placed on control (Cont; 16% fat, 3.85 kCal/g) or high fat (HF; 43% fat, 4.54 kCal/g) chow for 10 weeks. Baseline glucose tolerance (n=10, 16), MAP and HR (Radio-telemetry; n=7, 5), and 24hr urinary albumin excretion (n=3, 4) were measured. MAP and HR were measured throughout gestation and albumin excretion reassessed at gestational day (GA) 13.
After 10 wks of the diet, body weight of HF mice was 44% greater than Cont mice (32.7±0.9 vs 22.7±0.4g; P<0.001). Obese mice were hyperglycaemic (9.1±0.4 vs 7.6±0.5 mmol/L; P<0.05), glucose intolerant (716±43 vs 490±41AUC; P<0.001), had elevated MAP (105.7±1.3 vs 98.1±1.4mmHg; P<0.001), HR (548±8 vs 492±9bpm; P<0.001) and were albuminuric (4.53±0.62 vs 2.42±0.42μg/24h; P<0.05) compared to Cont mice. MAP and HR of obese mice remained elevated over Cont mice throughout pregnancy (Pdiet<0.01). 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. Albumin excretion increased 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 that persist throughout pregnancy without altering the normal adaptations of MAP and HR during pregnancy. Importantly, pregnancy exacerbates albuminuria in obese females suggesting that obesity might increase the risk of renal complications during pregnancy and lead to renal disease in later life.