The study demonstrates widespread expression of AT4 receptors in the kidneys across species and shows that their density is selectively altered by various models of renal dysfunction.
Abundant AT4 expression in animal kidneys should not yet change practice; leaves open therapeutic relevance in human renal disease.
Receptor autoradiography revealed that angiotensin AT(4) receptors were abundantly expressed in normal mammalian (mouse, rat, gerbil, guinea pig, rabbit) and avian (sparrow, chicken, turkey) kidneys and were more extensively distributed than previously reported (including proximal and distal segments of the nephron, interstitium, renal artery, vein, and ureter). Angiotensin AT(4) receptors were generally found to be more abundant than angiotensin AT(1) receptors in mammalian kidneys, whereas angiotensin AT((1-7)) receptors were not detected in either mammalian or avian kidneys. Rats subjected to various chronic treatments were found to preferentially decrease kidney AT(4) receptor density (furosemide, puromycin aminonucleoside, nitro-L-arginine methyl ester), decrease kidney AT(1) receptor density (bilateral ureteral obstruction), or increase kidney AT(1) receptor distribution in the inner medulla (water diuresis). These results indicate that the AT(4) receptor can be expressed in numerous cell types within the normal kidney of several species. Furthermore, several models of renal dysfunction and injury have been identified that selectively alter kidney AT(4) density and may potentially aid in elucidating the role of this novel angiotensin receptor system in renal function.
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Handa et al. (2001) studied this question.
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