Glomerular prostaglandin production in diabetic rats with renovascular hypertension

Abstract

A rat model combining two-kidney, one-clip (2K1C) renovascular hypertension and streptozotocin-induced diabetes mellitus was used to assess the pathogenetic significance of vasodilator prostaglandins in diabetic glomerular injury. Glomeruli isolated from normotensive diabetic rats produced greater than normal amounts of PGE2 and 6-keto PGF(1α) under in vitro incubation conditions. In 2K1C hypertensive-diabetic rats, glomeruli from unclipped kidneys (which are prone to accelerated diabetic glomerular injury) produced similarly elevated amounts of PGE2 and 6-keto PGF(1α), which significantly exceeded the levels produced by glomeruli from clipped kidneys (which are relatively protected from glomerular injury), despite exposure to a similar diabetic environment. In contrast, glomeruli from both unclipped an clipped kidneys of 2KIC hypertensive-non-diabetic rats produced normal amounts of PGE2 and 6-keto PGF(1α). These results suggests a correlation between vasodilator prostaglandin metabolism and susceptibility to diabetic glomerular injury, and illustrate that enhanced glomerular prostaglandin production is not an invariable metabolic consequence of hyperglycemia or insulin deficiency. The data also demonstrate that hemodynamic as wel as metabolic factors may influence glomerular prostaglandin metabolism in experimental diabetes mellitus.