Uteroplacental insufficiency programmes vascular dysfunction in non‐pregnant rats: compensatory adaptations in pregnancy
Authors: Mazzuca Marc Q. , Tare Marianne , Parkington Helena C. , Dragomir Nicoleta M. , Parry Laura J. , Wlodek Mary E. 
Published: May 2012

Key points

Uteroplacental insufficiency programmes uterine vascular dysfunction in female offspring born growth restricted. The vascular adaptations in these female offspring when they in turn become pregnant are poorly understood.

Females born small and later become pregnant have compensatory vascular adaptations, such that the increased uterine and renal arterial stiffness observed in the non‐pregnant state was resolved in late pregnancy.

Vascular smooth muscle and endothelial function was normal in pregnant growth restricted female offspring. There was a reduced sensitivity to angiotensin II, but an increased sensitivity to phenylephrine in uterine arteries during pregnancy, and enhanced endothelium‐mediated relaxation in uterine and mesenteric arteries. Importantly, arteries of growth restricted females adapted to these changes.

Pregnancy was associated with increased outside and internal diameters in uterine and mesenteric arteries, but not renal and femoral arteries, and being born growth restricted did not alter this process.

These findings may assist our understanding of the maternal vascular adaptations to pregnancy in growth restricted female offspring.

Abstract  Intrauterine growth restriction is a risk factor for cardiovascular disease in adulthood. We have previously shown that intrauterine growth restriction caused by uteroplacental insufficiency programmes uterine vascular dysfunction and increased arterial stiffness in adult female rat offspring. The aim of this study was to investigate vascular adaptations in growth restricted female offspring when they in turn become pregnant. Uteroplacental insufficiency was induced in WKY rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of pregnancy. F0 pregnant females delivered naturally at term. F1 Control and Restricted offspring were mated at 4 months of age and studied on day 20 of pregnancy. Age‐matched non‐pregnant F1 Control and Restricted females were also studied. Wire and pressure myography were used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in uterine, mesenteric, renal and femoral arteries of all four groups. Collagen and elastin fibres were quantified using polarized light microscopy and qRT‐PCR. F1 Restricted females were born 10–15% lighter than Controls (P < 0.05). Non‐pregnant Restricted females had increased uterine and renal artery stiffness compared with Controls (P < 0.05), but this difference was abolished at day 20 of pregnancy. Vascular smooth muscle and endothelial function were preserved in all arteries of non‐pregnant and pregnant Restricted rats. Collagen and elastin content were unaltered in uterine arteries of Restricted females. Growth restricted females develop compensatory vascular changes during late pregnancy, such that region‐specific vascular deficits observed in the non‐pregnant state did not persist in late pregnancy.