The present studies were designed (1) to examine the pattern of changes in
eicosanoid biosynthesis in isolated rat glomeruli, and (2) to correlate these changes with the previously observed alterations in renal perfusion and glomerular filtration rate which occur after
uranyl nitrate administration, a model of toxin-induced
acute renal failure. In the first part of this study, the in vitro and the in vivo effects of two
cyclooxygenase inhibitors were examined for their ability to inhibit rat glomerular
eicosanoid biosynthesis. Inhibition of
prostaglandin E2 and
prostaglandin F2 alpha generation by 1 mM
aspirin in vitro was 76 and 82%, respectively. Similar inhibitions of 85 and 72% of biosynthesis of the above-mentioned
lipids by 0.1 mM
indomethacin were also noted. Intraperitoneal administration of
aspirin (150 mg/kg) resulted in a significant inhibition of 88% or greater of
prostaglandin E2,
prostaglandin F2 alpha,
6-keto-prostaglandin F2 alpha, and
thromboxane B2 biosynthesis. These results indicated that the expected alterations produced under in vivo conditions were detectable by in vitro techniques used in this study. 24 h after the administration of
uranyl nitrate (25 mg/kg), significant increases in the biosynthesis of
prostaglandin E2 (124%) and
prostaglandin F2 alpha (88%) were observed when compared to the control values. No significant changes in
prostacyclin or
thromboxane formation were noted at this time. A further increase in the biosynthesis of
prostaglandin E2 (248%),
prostaglandin F2 alpha (262%), and a significant increase in
prostacyclin (120%), measured as 6-keto-prostaglandin F1 alpha, were noted at 48 h. No changes in
thromboxane B2 biosynthesis were noted. It is concluded that these data are consistent with the hypothesis that the increased glomerular biosynthesis of
vasodilator eicosanoids (i.e.,
prostaglandin E2 and
prostacyclin) may play a significant role in the homeostatic regulation of renal perfusion and glomerular filtration after acute toxic injury to the kidney.