Ontogeny of vascular angiotensin II receptor subtype expression in ovine development

Angiotensin II (ANG II) increases arterial pressure in fetal sheep and may modulate cardiovascular adaptation before and after birth. The type 1 angiotensin II receptor (AT₁R) predominates in adult vascular smooth muscle (VSM) and mediates vasoconstriction. In contrast, AT₂R predominate in fetal tissues and are not known to mediate contraction. Although sheep are commonly used to study cardiovascular development, the ontogeny and distribution of VSM ATR subtypes is unknown. We examined ATR binding characteristics and subtype expression across the umbilicoplacental vasculature and in aorta, carotid, and mesenteric arteries from fetal (n = 44; 126-145 d gestation) and postnatal (n = 65; 1-120 d from birth) sheep using plasma membranes from tunica media and tissue autoradiography. Binding density (B(max)) was similar throughout the umbilicoplacental vasculature (p = 0.5), but only external umbilical arteries and veins and primary placental arteries expressed AT₁R, whereas subsequent placental branches and fetal placentomes expressed only AT₂R. Systemic VSM B(max) and binding affinity did not change significantly during development (p > 0.1). Fetal systemic VSM, however, expressed only AT₂R, and binding was insensitive to GTPγS. Transition to AT₁R in systemic VSM began 2 wk postnatal and was completed by 3 mo. Before birth, umbilical cord vessels are the primary site of AT₁R expression in fetal sheep, and AT₂R seem to predominate in systemic VSM until 2-4 wk postnatal.