Distribution of Prostaglandins E2 and 6-Keto-FlQr Production in Dog Kidneys

Little is known about the distribution of prostaglandin E? (PGE?) and prostacyclin (PGLJ production in the canine kidney. To determine the basal and stimulated profiles of PGE^ and PGI2 production along the corticomedullary axis of the dog kidney, a slice (0.5 mm thick, 10-50 mg) was obtained from six equally spaced zones along the axis (zone 1, medullary crest; zones 2 and 3, inner medulla; zone 4, outer medulla; and zones 5 and 6, cortex) and was divided into equal halves. One half of the slice was incubated with Krebs-Ringer buffer containing arachidonic acid (6.6xlO~< M), bradykinin (9.4x10"' M), or indomethacin (10~ M), whereas the remaining half of each slice was similarly incubated in Krebs-Ringer buffer alone. The production of PGEj and 6-keto-PGFla (the stable metabolite of PGI2) was determined by radioimmunoassay. Under basal conditions, both PGF^ and 6-keto-PGFla were highest in the innermost zones of the inner medulla (PGEj, 3,328±549 pg/mg; 6-keto-PGF,,,, 1,611±129 pg/mg) and decreased exponentially to low levels in the cortex (PGEj, undetectable; 6keto-PGFla, 13±2 pg/mg); this production was inhibited by indomethacin. Arachidonic acid significantly increased the production of PGEj in all zones of the kidney and the production of 6-keto-PGF,a only in zones 3 -6 . Bradykinin significantly stimulated production of PGE? in zones 1, 3, and 4 and 6-keto-PGFlCT in zones 4-6 , suggesting that in the inner medulla, unlike the cortex, 6-keto-PGF,a production was saturated under basal conditions and could not be stimulated further. PGEj production, on the other hand, was increased throughout all zones of the kidney with excess substrate (arachidonic acid) but was most sensitive to stimulation by bradykinin in the inner medulla. (Hypertension 1990;15(suppl I):I-107-I-lll)