ONTOGENIC EXPRESSION OF RENAL AND HEPATIC ANGIOTENSIN-II RECEPTOR GENES IN THE RAT

In addition to its well-characterized renal hemodynamic effects, angio tensin II (Ang II) promotes growth of cultured glomerular and tubular cells, suggesting a possible role in renal development. To better defi ne potential developmental effects of Ang II, we examined the expressi on of Ang II receptors in embryonic (E19) and postnatal(1, 2, 3, 10 da ys, 6 weeks, 3 and 9 months) rat kidneys, using in situ autoradiograph y and the nonpeptide antagonists losartan and PD-123177 to identify re ceptor subtypes. At E19, I-125-[Sar(1), Ile(8)]Ang II binding was equa lly reduced by losartan and PD-123177, indicating the presence of both AT(1) and AT(2) receptors. A progressive increase in Ang II receptor density occurred after birth, reaching a plateau at day 10. At that ti me, the AT(1) subtype predominated and was virtually the sole subtype present thereafter. Ang II receptor density and AT(1) mRNA levels decr eased in aging rats. Total AT(1) receptor mRNA levels in both kidney a nd liver were determined by Northern hybridization analysis using a ra diolabeled AT(1) anti-sense cRNA probe. In both tissues, ATI mRNA leve ls increased rapidly following birth, reached a maximum on day 10 and decreased thereafter. To further characterize the ontogenic effects on AT(1) gene expression, renal AT(1A) and AT(1B) receptor mRNA isoforms were determined by reverse transcription and the polymerase chain rea ction. No significant differences were observed during maturation betw een the relative levels of AT(1A) and AT(1B) mRNAs, with the AT(1A) is oform accounting for approximately 78% at any time point. Thus, renal AT(1) receptor density increases rapidly after birth, in association w ith an increase in both AT(1A) and AT(1B) receptor gene expression. As the predominant receptor isoform in the adult kidney, the AT(1A) rece ptor may account for the majority of the effects of Ang II on glomerul ar and tubular function.