Effect of experimental diabetes on glomerular filtration rate and glomerular prostanoid production in the rat.

Abstract

Glomerular hyperfiltration is an early functional renal lesion seen both in experimental and human diabetes mellitus. This increase in the glomerular filtration rate has been thought to be mediated, in part, by changes in vasoregulatory hormones such as the prostanoids. The present study was designed to measure glomerular prostanoid production in rats with experimental diabetes to determine whether the biochemical changes in prostanoid production could be consistent with the hemodynamic alterations noted. Sprague-Dawley rats were studied either 7 or 28 days after intravenous streptozotocin administration (60 mg/kg). Measurements of the glomerular filtration rate were performed in two groups of diabetic animals 28 days after streptozotocin administration: one group with intact prostanoid production, the other having received a cyclooxygenase inhibitor for the 4-week period. Similar studies were performed in nondiabetic control rats. Measurements of glomerular prostanoid production were performed in control and diabetic animals 7 days after streptozotocin administration. The results of these studies indicate that experimental diabetes mellitus is associated with an increase in the glomerular filtration rate and that this increase can be blocked by the administration of a cyclooxygenase inhibitor. In addition, the determination of levels of various glomerular prostanoids indicated an increased production of prostacyclin and a decreased production of thromboxane during this period of hyperfiltration. Thus, these data support the premise that altered prostanoid biosynthesis may be one of the biochemical mediators of the hyperfiltration seen in early experimental diabetes mellitus.