Early streptozotocin-diabetes mellitus downregulates rat kidney AT2receptors

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Abstract
The interaction of ANG II with intrarenal AT1receptors has been implicated in the progression of diabetic nephropathy, but the role of intrarenal AT2receptors is unknown. The present studies determined the effect of early diabetes on components of the glomerular renin-angiotensin system and on expression of kidney AT2receptors. 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) AT1receptor protein expression (AT1Aand AT1B) was increased in D rats, with no change in glycosylated (53-kDa) AT1receptor protein or in AT1receptor mRNA. By contrast, STZ diabetes caused a significant decrease in glomerular AT2receptor protein expression (47.0 ± 6.5% of C; P < 0.001; n = 6), with partial reversal in D+I rats. In normal rat kidney, AT2receptor 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 AT2receptor 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. AT2receptors are present in glomeruli and are downregulated in early diabetes, as are all kidney AT2receptors. Our data suggest that alterations in the balance of kidney AT1and AT2receptor expression may contribute to ANG II-mediated glomerular injury in progressive diabetic nephropathy.