Renal AT1 Receptor Protein Expression During the Early Stage of Diabetes Mellitus

Experiments were performed to evaluate the hypothesis that the early stage of Type 1 diabetes mellitus (DM) increases renal angiotensin II (AngII) concentration and angiotensin type 1 (AT1) receptor protein levels. Nineteen or twenty days after vehicle (Sham rats) or streptozotocin (STZ rats) treatment, plasma [AngII] was higher in STZ rats (152±23 fmol/ml) than in Sham rats (101±7 fmol/ml); however, kidney [AngII] did not differ between groups. AT1 receptor protein expression was greater in STZ kidneys than in Sham kidneys. This increase was restricted to the cortex, where AT1 protein levels were elevated by 77±26% (42 kDa) and 101±16% (58 kDa) in STZ kidneys. Immunohistochemistry revealed this effect to be most evident in distal nephron segments including the connecting tubule/cortical collecting duct. Increased renal cortical AT1 receptor protein and circulating AngII levels are consistent with an exaggerated AngII-dependent influence on renal function during the early stage of DM in the rat.