The changes in angiotensin II receptor subtypes, type 1 (AT1) and type 2 (AT2) binding, and AT1 mRNA levels during development were studied in the rat kidney using autoradiographic and in situ hybridization techniques. Autoradiographic analysis of 125I-[Sar1,Ile8]Ang II binding to slide-mounted kidney sections from 2 and 5 day-old rats discerned AT2 binding sites associated with advancing tubules and ampullae of the ureteric bud, and in the metanephric mass in the nephrogenic zone of the cortex. AT1 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 AT1 receptor binding over glomeruli in renal cortex and in the inner stripe of the outer medulla. AT1 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, AT1 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 AT1 receptor mRNA is developmentally regulated in rat kidney and its expression in the cortex precedes that of AT1 receptor ligand binding. The temporal pattern of expression of binding for both receptor subtypes suggests that while AT2 receptors may be involved in cell proliferation and early differentiation of the nephron, AT1 receptors have a dual role, early in nephron differentiation and later in development in renal function.

The effects of chronic stress on the renin-angiotensin-aldosterone system were studied by analysis of plasma hormone levels, kidney renin mRNA levels, adrenal angiotensin II receptors, and steroidogenesis in rats subjected to repeated immobilization (2 h daily) or intraperitoneal injections of 1.5 M NaCl for 14 d. 24 h after the last stress in both stress models, plasma aldosterone levels were reduced in spite of significant increases in plasma renin activity. Repeatedly intraperitoneal hypertonic saline-injected rats showed plasma renin activity responses to acute immobilization similar to controls, but markedly reduced plasma aldosterone responses. Concomitant with the increases in plasma renin activity, renin mRNA levels in the kidney were significantly increased in intraperitoneal hypertonic saline-injected rats, and these increases were prevented by ,B-adrenergic receptor blockade with propranolol. In isolated adrenal glomerulosa cells from chronically stressed rats, maximum aldosterone responses to angiotensin II, ACTH, and 8-Br-cAMP were significantly decreased, whereas pregnenolone responses were increased. P450-aldosterone synthetase mRNA levels and binding of '"I-[Sar',Ile8]angiotensin II were significantly reduced in the adrenal zona glomerulosa of stressed rats. These studies show that chronic repeated stress leads to renin stimulation due to sympathetic activation, and inhibition of aldosterone secretion due to inhibition of the late steroidogenic pathway. The data provide evidence for a role of chronic stress in the development of hyperreninemic hypoaldosteronism. (J. Clin. Invest. 1995. 96:1512-1519

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