Elevated vascular resistance and afterload reduce the cardiac output response to dobutamine in early growth-restricted rats in adulthood

Abstract

Epidemiological studies have linked intra-uterine growth restriction (IUGR) with an increased risk of CVD later in life. The aim of the present study was to examine the effect of maternal protein restriction on cardiac function in adulthood during dobutamine (DOB) stimulation. IUGR was induced in Wistar Kyoto dams through administration of a low-protein diet (LPD; 8.7 % casein) during pregnancy and lactation; the control group received a normal-protein diet (NPD; 20 % casein). At 14 weeks of age, cardiac function was assessed in male and female NPD (eight females and eight males) and LPD offspring (ten females and ten males) by pressure volumetry using an anaesthetised closed-chest approach. We determined mean arterial pressure (MAP), heart rate and left ventricular pressure-volume indices under baseline conditions and DOB stimulation (2 and 4 μg/kg per min). During β-adrenergic activation in LPD offspring, increases in cardiac output (CO, P < 0.018) and stroke volume (SV, P < 0.005) were attenuated in comparison with NPD offspring, while increases in ejection fraction and the maximal rate of ventricular pressure development were not affected. LPD females maintained a smaller end-diastolic volume (P < 0.017). MAP did not differ between the groups and did not change significantly during DOB infusion. Arterial elastance and total peripheral resistance decreased in all rats but remained significantly elevated in LPD offspring (P < 0.015 and < 0.01). Early growth restriction did not affect ventricular contractility but led to an increased afterload and impaired the ability to increase SV and CO during β-adrenergic stimulation.