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Am J Physiol Renal Physiol (May 7, 2002). doi:10.1152/ajprenal.00313.2001
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Articles in PresS, published online ahead of print May 7, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00313.2001
Submitted on October 11, 2001
Accepted on April 15, 2002

AngII AT1 and AT2 Receptors in Developing Kidney of Normal Microswine

Susan P Bagby1*, Susan P Bagby2, Linda S LeBard1, Linda S LeBard2, Zaiming Luo1, Zaiming Luo2, Bryan E Ogden3, Bryan E Ogden4, Christopher L Corless5, Christopher L Corless6, Elizabeth D McPherson1, Elizabeth D McPherson7, Robert C Speth8, and Robert C Speth9

1 Deparment of Medicine, Oregon Health & Science University and Portland VA Medical Center, Portland, Oregon, USA
2 Nephrology Research, Oregon Health & Sceinces University, Portland, Oregon, USA
3 Department of Comparative Medicine, Oregon Health & Science University and Portland VA Medical Center, Portland, Oregon, USA
4 Comparitive Medicine, OHSU, Portland, Oregon, USA
5 Department of Pathology, Oregon Health & Science University and Portland VA Medical Center, Portland, Oregon, USA
6 Pathology, OHSU, Portland, Oregon, USA
7 Medicine/Nephrology, Oregon Health & Science University, Portland, Oregon, USA
8 Department of Veterinary and Comparative Anatomy and Pharmacology & Physiology, Washington State University, School of Veterinary Medicine, Pullman, WA, USA
9 Veterinary and Comparative Anatomy and Pharmacology & Physiology, Washington State University, Pullman, WA, USA

* To whom correspondence should be addressed. E-mail: bagbys{at}ohsu.edu.

To identify an appropriate model of human renin+angiotensin system (RAS) involvement in fetal origins of adult disease, we quantitated renal AngII receptors in fetal (GD 90, n=14), neonatal (3-wk, n=5), and adult (6-mo, n=8) microswine by autoradiography (125I-Sar1Ile8AngII + cold CGP 42112 for AT1R, 125I-CGP 42112 for AT2R) and by whole-kidney radioligand binding. AT1R binding exhibited 10-fold increase postnatally (p<.001) with maximal postnatal density in glomeruli and lower-density AT1R in extra-glomerular cortex and outer medulla. Cortical levels of AT2R by autoradiography fell with age from ~= 5000 fmol/g in fetal kidneys to ~= 60% and 20% of fetal levels in neonatal and adult cortex respectively (p<.0001). Swine renal AT2R binding mimicked that described in primate - but not rodent - species: dense AT2R confined to discrete cortical structures which included pre- and juxta- (but not intra-) glomerular vasculature. Results provide a quantitative assessment of AngII receptors in developing pig kidney and document concordance of pig and primate in developmental regulation of renal AT1 and AT2 receptors.




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