Expression of AT2 receptors in the developing rat fetus.

TLDR

Angiotensin II, beyond its classic cardiovascular roles, is increasingly recognized for influencing cellular growth. The study aimed to map angiotensin II receptor subtypes during fetal and neonatal development and determine their cellular distribution. Researchers performed in situ receptor binding on sagittal frozen sections of fetal and neonatal rats, visualizing 125I‑[Sar1,Ile8]‑angiotensin II binding via film and emulsion autoradiography. AT2 receptors were transiently expressed in fetal mesenchyme, peaking at embryonic days 19–21, remaining stable 30 min after birth but declining 12 h postpartum, while AT1 receptors appeared in placenta and adult‑like organs, indicating a developmental role for angiotensin II.

Abstract

Angiotensin II is known primarily for its effects on blood pressure and electrolyte homeostasis, but recent studies suggest that angiotensin II may play a role in the regulation of cellular growth. This study was undertaken to identify the angiotensin II receptor subtypes expressed during fetal and neonatal development and to characterize their cellular localization. Using an in situ receptor binding assay on sagittal frozen sections of fetal and neonatal rats, bound 125I-[Sar1,Ile8]-angiotensin II was visualized by film and emulsion autoradiography. Bound radioligand was detected by E11 (embryonic day 11) and maximal binding occurred by E19-21. Radioligand binding remained unaltered 30 min after birth, whereas a noticeable and stable decrease was observed 12 h postparturition. The highly abundant angiotensin II receptors were shown to be AT2 by the marked reduction in radioligand binding achieved with PD123177 (10(-7)M), a specific AT2 receptor antagonist, whereas DuP 753 (10(-5)M), an AT1 receptor antagonist, had little effect. Emulsion autoradiography showed radioligand binding in the undifferentiated mesenchyme of the submucosal layers of the intestine and stomach, connective tissue and choroid surrounding the retina, subdermal mesenchyme adjacent to developing cartilage, diaphragm, and tongue. Residual AT2 receptors were found on the dorsal subdermal region of the tongue 72 h after birth. AT1 receptors were detected in the placenta at E13 and in the aorta, kidney, lung, liver, and adrenal gland at E19-21, consistent with an adult distribution. The transient expression of AT2 receptors in the mesenchyme of the fetus suggests a role of angiotensin II in fetal development.