DEVELOPMENTAL-CHANGES IN ANGIOTENSIN-II RECEPTOR SUBTYPES AND AT(1) RECEPTOR MESSENGER-RNA IN RAT-KIDNEY

The changes in angiotensin II receptor subtypes, type 1 (AT(1)) and type 2 (AT(2)) binding, and AT(1) mRNA levels during development were studied in the rat kidney using autoradiographic and in situ hybridization techniques. Autoradiographic analysis of I-125-[Sar(1), Ile(8)]Ang II binding to slide-mounted kidney sections from 2 and 5 day-old rats discerned AT(2) binding sites associated with advancing tubules and ampullae of the ureteric bud, and in the metanephric mass in the nephrogenic zone of the cortex. AT(1) binding was present in the metanephric mass and immature glomeruli on days 2, 5 and 7 after birth. Differentiating and mature kidneys of 14-day, 21-day and 14-week old adult rats had solely AT(1) receptor binding over glomeruli in renal cortex and in the inner stripe of the outer medulla. AT(1) mRNA was expressed discretely as early as 2 days of age in the immature glomeruli and in a diffuse radiating pattern in the renal cortex. In the medulla, AT(1) receptor mRNA expression appeared discretely on day 7 and reached peak levels on day 21 in the inner stripe of the outer medulla. The data indicate that AT(1) receptor mRNA is developmentally regulated in rat kidney and its expression in the cortex precedes that of AT(1) receptor ligand binding. The temporal pattern of expression of binding for both receptor subtypes suggests that while AT(2) receptors may be involved in cell proliferation and early differentiation of the nephron, AT(1) receptors have a dual role, early in nephron differentiation and later in development in renal function.