Alteration of endothelin-1 concentration in STZ-induced diabetic rat nephropathy: Effects of a PGI₂ derivative

Background: Recently, an endothelin (ET-1) with a potent vasoconstrictive activity and stimulative activity of vascular muscular cell growth was discovered and blood ET-1 levels were higher in diabetic patients than in healthy subjects, suggesting that high ET-1 levels assist development and progression of diabetic microangiography. Methods: We examined renal function, and serum and tissue ET-1 levels in streptozotocin (STZ)-induced diabetic rats treated with a prostaglandin (PG) I₂ derivative to investigate the effect of PGI₂ in diabetic vascular disturbance. Results: Renal weight, urinary albumin, urinary N-acetyl-β,D-glucosaminidase (NAG) and serum ET-1 levels increased in STZ-induced diabetic rats, and a tendency to increase in renal tissue ET-1 levels was observed. Furthermore, electron-microscopic findings in the kidneys showed mesangial cell proliferation and mesangial matrix expansion which might be caused by diabetic nephropathy. The PGI₂ derivative reduced urinary albumin and NAG levels in STZ-induced rats. It was considered, therefore, that the PGI₂ derivative is effective in diabetic nephropathy. As the PGI₂ derivative also reduced renal tissue ET-1 levels, improvement of diabetic nephropathy partially was considered to result from the reduction of renal tissue ET-1 levels. Conclusion: In STZ-induced rats, increased serum ET-1 levels and a tendency to increase in renal tissue ET-1 levels were associated with increases in urinary albumin and NAG levels, and these levels were decreased by a PGI₂ derivative. These findings suggested that increased ET-1 concentrations assist development and progression of diabetic nephropathy, especially diabetic microangiopathy, and the PGI₂ derivative may be effective for inhibition of diabetic microangiopathy mediated by reduction of ET-1 concentrations.