Does endothelin play a role in the pathogenesis of early diabetic nephropathy?

Endothelin-1 (ET-1) causes dramatic vasoconstriction and reduction of renal blood flow, with a decreased glomerular filtration rate (GFR). Early diabetic nephropathy is characterized by elevation of GFR and the formation of intrarenal microaneurysms. However, the mechanisms are unclear. To elucidate the pathophysiologic significance of urinary ET-1 in early diabetic nephropathy, the 24-h urinary excretion of ET-1 in 12 normal subjects and 20 patients with newly diagnosed type 2 diabetes mellitus were determined by a highly sensitive radioimmunoassay. The 24-h urinary ET-1 excretion in patients with diabetes mellitus (14.2 +/- 3.1 pmol, mean +/- SEM) was significantly lower (p < 0.05) than that of normal subjects (25.0 +/- 3.7 pmol). This decrease in urinary excretion of ET-1 in patients with recent-onset diabetes mellitus suggests a possible role of ET-1 in the pathogenesis of early diabetic nephropathy.