Early streptozotocin-diabetes mellitus downregulates rat kidney [AT.sub.2] receptors

Early streptozotocin-diabetes mellitus downregulates rat kidney [AT.sub.2] receptors. Am J Physiol Renal Physiol 280: F254-F265, 2001.--The interaction of ANG II with intrarenal [AT.sub.2] receptors has been implicated in the progression of diabetic nephropathy, but the role of intrarenal [AT.sub.2] receptors is unknown. The present studies determined the effect of early diabetes on components of the glomerular renin-angiotensin system and on expression of kidney [AT.sub.2] receptors. Three groups of rats were studied after 2 wk: 1) control (C), 2) streptozotocin (STZ)-induced diabetic (D), and 3) STZ-induced diabetic with insulin implant (D+I), to maintain normoglycemia. By competitive RT-PCR, early diabetes had no significant effect on glomerular mRNA expression for renin, angiotensinogen, or angiotensin-converting enzyme (ACE). In isolated glomeruli, nonglycosylated (41-kDa) [AT.sub.1] receptor protein expression ([AT.sub.1A] and [AT.sub.1B]) was increased in D rats, with no change in glycosylated (53-kDa)[AT.sub.1] receptor protein or in [AT.sub.1] receptor mRNA. By contrast, STZ diabetes caused a significant decrease in glomerular [AT.sub.2] receptor protein expression (47.0 [+ or -] 6.5% of C; P [is less than] 0.001; n = 6), with partial reversal in D+I rats. In normal rat kidney, [AT.sub.2] receptor immunostaining was localized to glomerular endothelial cells and tubular epithelial cells in the cortex, interstitial, and tubular cells in the outer medulla, and inner medullary collecting duct cells. STZ diabetes caused a significant decrease in [AT.sub.2] receptor immunostaining in all kidney regions, an effect partially reversed in D+I rats. In summary, early diabetes has no effect on glomerular mRNA expression for renin, angiotensinogen, or ACE. [AT.sub.2] receptors are present in glomeruli and are downregulated in early diabetes, as are ell kidney [AT.sub.2] receptors. Our data suggest that alterations in the balance of kidney [AT.sub.1] and [AT.sub.2] receptor expression may contribute to ANG II-mediated glomerular injury in progressive diabetic nephropathy. renin-angiotensin system; glomerulus; immunohistochemistry; hyperglycemia; angiotensin type 1 receptor