Angiotensin II Receptor Type 1 Gene Expression in Human Glomerulonephritis and Diabetes Mellitus

. The renin-angiotensin system plays an important role in the progression of chronic renal disease. Although the expression of renin and angiotensin-converting enzyme in experimental and human renal disease has been well characterized, no information is available regarding human angiotensin type 1 (AT 1 ) receptor expression. The net effect of renin depends on AT 1 receptor expression, among other factors. Receptor expression was determined in renal biopsy samples (including all tissue components) and isolated glomeruli from patients with glomerulonephritis (GN) or diabetic nephropathy (non-insulin-dependent diabetes mellitus). Biopsy samples and isolated glomeruli from tumor-free tissue from tumor nephrectomies served as controls. Human AT 1 receptor gene expression was determined by quantitative reverse transcription-PCR, using an AT 1 receptor deletion mutant as the internal standard. In whole biopsy samples from 37 patients with various types of GN, AT 1 receptor mRNA levels were lower, compared with nine control biopsy samples ( P < 0.001). AT 1 receptor mRNA levels were also significantly lower ( P < 0.001) in eight samples from patients with diabetic nephropathy. In microdissected glomeruli, AT 1 receptor gene expression was significantly lower in samples from patients ( n = 22) with various types of GN, compared with 12 microdissected tumor nephrectomy control samples ( P < 0.0023). It is concluded that AT 1 receptor mRNA expression is low in glomeruli of patients with chronic renal disease. This may reflect a regulatory response to (inappropriately) high intrarenal angiotensin II concentrations.