Stimulation of prostaglandin biosynthesis in the renal papilla by hypertonic mediums

The effect of hypertonic buffers on prostaglandin biosynthesis was studied in rat renal papillae in vitro. Prostaglandin (PG) production was measured with combined gas chromatography-mass spectrometry or bioassayed with the rat fundus strip. Hypertonic buffers (450-1,500 mosmol/liter) were prepared by addition of sucrose, NaCl, or urea to regular buffer and added to the incubate after a base-line prostaglandin output had been established. PGE₂, PGF(2α), and PGD₂ were all released in greatly increased amounts by papillae exposed to hypertonic NaCl. Hypertonic sucrose buffer stimulated prostaglandin output to the same extent as NaCl but comparable concentrations of urea produced weaker stimulations. The stimulation of prostaglandin biosynthesis by hypertonic saline was time and concentration dependent. Tissues incubated with [¹⁴]arachidonic acid produced prostaglandins of greatly lowered specific activity when buffers were made hypertonic and the stimulation of prostaglandin output was completely blocked by treatment of the tissue with indomethacin or mefenamic acid. These studies indicate that hypertonic mediums increased the production of renomedullary prostaglandins by increasing the amount of available free arachidonic acid. Incubates of renal papillae from rabbits and dogs also produced significantly increased amounts of prostaglandins on exposure to hypertonic mediums. It is concluded that extracellular osmolarity may be a regulator of prostaglandin biosynthesis in the renal medulla.