ANG II AT(1) and AT(2) receptors in developing kidney of normal microswine.
To identify an appropriate model of human renin-angiotensin system (RAS) involvement in fetal origins of adult disease, we quantitated renal ANG II AT(1) and AT(2) 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 ((125)I-labeled [Sar(1)Ile(8)]ANG II+cold CGP-42112 for AT1R, (125)I-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 with 5,000 fmol/g in fetal kidneys to congruent with 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.
Bagby
Susan P
SP
Department of Medicine, Oregon Health and Science University, and Portland Veterans Affairs Medical Center, 97201-2940, USA. bagbys@ohsu.edu
LeBard
Linda S
LS
Luo
Zaiming
Z
Ogden
Bryan E
BE
Corless
Christopher
C
McPherson
Elizabeth D
ED
Speth
Robert C
RC
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D005260:Female; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D007668:Kidney / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism; D011247:Pregnancy; D011869:Radioligand Assay; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II