Differential expression of angiotensin II receptors during early renal morphogenesis

Angiotensin II (ANG II) and its receptors, AT(1) and AT(2), may modulate kidney development. To define the temporal and spatial distribution of AT(1) and AT(2) receptors and their mRNAs during nephrogenesis, fetal, newborn, and adult rat kidneys were studied using reverse transcription-polymerase chain reaction and radioligand binding autoradiography. AT(1) expression was minimal at embryonic day 14 (E14), highly expressed at E20, and persisted into adulthood. Conversely, AT(2) expression was easily detected from E14 through postnatal day 7 but was undetectable by postnatal day 28. At E14, 76% of the receptors were AT(2), 24% were AT(1), and both were found in the undifferentiated mesenchyme. By E17, AT(1) comprised 40% of the receptors and localized to mature nephron segments, whereas AT(2) remained within both condensed mesenchyme and differentiating epithelia. The dissociation constants for AT(1) and AT(2) were 0.45 +/- 0.09 nM and 0.73 +/- 0.15 nM, respectively, at E17, similar to adult values. By E20, AT(1) and AT(2) colocalized to the outer medullary stripe, deep nephrons, medullary rays, and blood vessels, while AT(2) continued to predominate in the actively differentiating cortex. The presence of both subtypes of receptors capable of binding ANG II during early nephrogenesis and the time-dependent and structure-specific regulation of receptor localization confirm a regulated developmental program for receptor expression and suggest important roles for AT(1) and AT(2) in renal morphogenesis.