Protein increases glomerular eicosanoid production and activity of related enzymes

We examined the in vitro production of PGE₂, 6-keto PGF_1α and TxB₂ by isolated glomeruli from rats fed a low (6% casein) or a high (40% casein) protein diet for approximately eight weeks. Glomeruli from high protein-fed rats produced significantly greater amounts of PGE₂, 6-keto PGF_1α and TxB₂ under basal conditions and in response to the addition of 100 nM angiotensin II (Ang II) than glomeruli from low protein-fed rats. To elucidate the mechanisms by which greater protein intake enhanced the glomerular production of eicosanoids, we explored phospholipase (A₂ and C) and cyclooxygenase activity in glomeruli isolated from low- or high-protein fed rats. PE-specific PLA₂ activities were significantly increased in glomeruli from rats fed a high protein diet when compared to a low protein diet. On the other hand, PC-specific PLA₂ activities were significantly decreased in glomeruli from rats fed a high protein diet. No significant difference in PIP₂-PLC activities was detected between glomeruli of the two dietary groups. The cyclooxygenase content and activity was significantly greater in glomeruli from rats fed a high protein diet than in glomeruli from rats fed a low protein diet. Glomeruli of rats fed a 50/50 mixture of the diets (23% casein) had amounts and activity of cyclooxygenase and activities of PE-specific PLA₂ intermediate between those of high and low protein-fed animals. In conclusion, increased synthesis of eicosanoids by glomeruli from rats fed a high protein diet may be mediated by increases in the amount and activity of cyclooxygenase coupled with enhanced activity of PE-specific PLA₂.