ANG II AT1 and AT2 receptors in developing kidney of normal microswine

Abstract

To identify an appropriate model of human renin-angiotensin system (RAS) involvement in fetal origins of adult disease, we quantitated renal ANG II AT1 and AT2 receptors (AT1R and AT2R, respectively) in fetal (90-day gestation, n = 14), neonatal (3-wk, n = 5), and adult (6-mo, n = 8) microswine by autoradiography (125I-labeled [Sar1Ile8]ANG II+cold CGP-42112 for AT1R,125I-CGP-42112 for AT2R) and by whole kidney radioligand binding. The developmental pattern of renal AT1R in microswine, like many species, exhibited a 10-fold increase postnatally ( P < 0.001), with maximal postnatal density in glomeruli and lower density AT1R in extraglomerular cortical and outer medullary sites. With aging, postnatal AT1R glomerular profiles increased in size ( P < 0.001) and fractional area occupied ( P < 0.04), with no change in the number per unit area. Cortical levels of AT2R by autoradiography fell with age from ≅5,000 fmol/g in fetal kidneys to ≅60 and 20% of fetal levels in neonatal and adult cortex, respectively ( P < 0.0001). The pattern of AT2R binding in postnatal pig kidney mimicked that described in human and simian, but not rodent, species: dense AT2R confined to discrete cortical structures, including pre- and juxtaglomerular, but not intraglomerular, vasculature. Our results provide a quantitative assessment of ANG II receptors in developing pig kidney and document the concordance of pigs and primates in developmental regulation of renal AT1R and AT2R.