Ontogenic Expression of Renal and Hepatic Angiotensin II Receptor Genes in the Rat

Abstract

In addition to its well-characterized renal hemodynamic effects, angiotensin II (Ang II) promotes growth of cultured glomerular and tubular cells, suggesting a possible role in renal development. To better define potential developmental effects of Ang II, we examined the expression of Ang II receptors in embryonic (E19) and postnatal (1, 2, 3, 10 days, 6 weeks, 3 and 9 months) rat kidneys, using in situ autoradiography and the nonpeptide antagonists losartan and PD-123177 to identify receptor subtypes. At E19, ¹²⁵I-[Sar¹, Ile⁸]Ang II binding was equally reduced by losartan and PD-123177, indicating the presence of both AT₁ and AT₂ receptors. A progressive increase in Ang II receptor density occurred after birth, reaching a plateau at day 10. At that time, the AT₁ subtype predominated and was virtually the sole subtype present thereafter. Ang II receptor density and AT₁ mRNA levels decreased in aging rats. Total AT₁ receptor mRNA levels in both kidney and liver were determined by Northern hybridization analysis using a radiolabeled AT₁ anti-sense cRNA probe. In both tissues, AT₁ mRNA levels increased rapidly following birth, reached a maximum on day 10 and decreased thereafter. To further characterize the ontogenic effects on AT₁ gene expression, renal AT_1A and AT_1B receptor mRNA isoforms were determined by reverse transcription and the polymerase chain reaction. No significant differences were observed during maturation between the relative levels of AT_1A and AT_1B mRNAs, with the AT_1A isoform accounting for approximately 78% at any time point. Thus, renal AT₁ receptor density increases rapidly after birth, in association with an increase in both AT_1A and AT_1B receptor gene expression. As the predominant receptor isoform in the adult kidney, the AT_1A receptor may account for the majority of the effects of Ang II on glomerular and tubular function.