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Am J Physiol Renal Physiol 283: F755-F764, 2002. First published May 7, 2002; doi:10.1152/ajprenal.00313.2001
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Vol. 283, Issue 4, F755-F764, October 2002

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

Susan P. Bagby1, Linda S. LeBard1, Zaiming Luo1, Bryan E. Ogden2, Christopher Corless3, Elizabeth D. McPherson1, and Robert C. Speth4

Departments of 1 Medicine, 2 Comparative Medicine, and 3 Pathology, Oregon Health and Science University, and Portland Veterans Affairs Medical Center, Portland, Oregon 97201-2940; and 4 Departments of Veterinary and Comparative Anatomy and of Pharmacology and Physiology, School of Veterinary Medicine, Washington State University, Pullman, Washington 99164-6520

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 congruent 5,000 fmol/g in fetal kidneys to congruent 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.

developing kidney; AT1; AT2; quantitative autoradiography; swine


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