Angiotensin II receptor type 1 gene expression in human glomerulonephritisand diabetes mellitus

The renin-angiotensin system plays an important role in the progression of chronic renal disease. Although the expression of renin and angiotensin-con verting enzyme in experimental and human renal disease has been well charac terized, 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 ren al biopsy samples (including all tissue components) and isolated glomeruli from patients with glomerulonephritis (GN) or diabetic nephropathy (non-ins ulin-dependent diabetes mellitus). Biopsy samples and isolated glomeruli fr om tumor-free tissue from tumor nephrectomies served as controls. Human AT( 1) receptor gene expression was determined by quantitative reverse transcri ption-PCR, using an AT, receptor deletion mutant as the internal standard. In whole biopsy samples from 37 patients with various types of GN, AT(1) re ceptor mRNA levels were lower, compared with nine control biopsy samples (P < 0.001). AT, receptor mRNA levels were also significantly lower (P < 0.00 1) in eight samples from patients with diabetic nephropathy. In microdissec ted glomeruli, AT(1) receptor gene expression was significantly lower in sa mples from patients (n = 22) with various types of GN, compared with 12 mic rodissected tumor nephrectomy control samples (P < 0.0023). It is concluded that AT(1) receptor mRNA expression is low in glomeruli of patients with c hronic renal disease. This may reflect a regulatory response to (inappropri ately) high intrarenal angiotensin n concentrations.