Restriction of placental and fetal growth in sheep alters fetal blood pressure responses to angiotensin II and captopril

Abstract

1. We have measured arterial blood pressure between 115 and 145 days gestation in normally grown fetal sheep (control group; n = 16) and in fetal sheep in which growth was restricted by experimental restriction of placental growth and development (PR group; n = 13). There was no significant difference in the mean gestational arterial blood pressure between the PR (42.7 +/- 2.6 mmHg) and control groups (37.7 +/- 2.3 mmHg). Mean arterial blood pressure and arterial PO2 were significantly correlated in control animals (r = 0.53, P < 0.05, n = 16), but not in the PR group. 2. There were no changes in mean arterial blood pressure in either the PR or control groups in response to captopril (7.5 microg captopril min-1; PR group n = 7, control group n = 6) between 115 and 125 days gestation. After 135 days gestation, there was a significant decrease (P < 0.05) in the fetal arterial blood pressure in the PR group but not in the control group during the captopril infusion (15 microg captopril min-1; PR group n = 7, control group n = 6). 3. There was a significant effect (F = 14.75; P < 0.001) of increasing doses of angiotensin II on fetal diastolic blood pressure in the PR and control groups. The effects of angiotensin II were different (F = 8.67; P < 0.05) in the PR and control groups at both gestational age ranges. 4. These data indicate that arterial blood pressure may be maintained by different mechanisms in growth restricted fetuses and normally grown counterparts and suggests a role for the fetal renin-angiotensin system in the maintenance of blood pressure in growth restricted fetuses.

Figure 1. The relationship between arterial P_O2 and mean arterial blood pressure in control and PR fetal sheep

The relationship between the mean gestational arterial P_O2 values and mean arterial blood pressure in control fetal sheep (▪, n = 16; A) and PR fetal sheep (^, n = 13; B). There was a significant correlation between arterial P_O2 and blood pressure in the control fetal sheep (r = 0.53, P < 0.05).

Figure 2. The effect of captopril on mean arterial blood pressure in control and PR fetal sheep

The arterial blood pressure response (mean ±s.e.m.) to a 4 h captopril infusion (15 μg min⁻¹) in control fetuses (▪, n = 6) and PR fetuses (^, n = 7) between 135 and 145 days gestation. *P < 0.05, significantly different from pre-infusion values.

Figure 3. The effect of angiotensin II on diastolic blood pressure in control and PR fetal sheep

The diastolic blood pressure response (means ±s.e.m.) to increasing bolus doses of AII (0.01–4.0 μg kg⁻¹) in control fetal sheep (n = 8; black histograms; A) and PR fetal sheep (n = 9; open histograms; B) between 115 and 145 days gestation. Different letters denote significant differences (P < 0.05) between mean values.