Increased prostaglandin synthesis in the unclipped kidney of one-kidney, one clip hypertensive rats.

Abstract

Reversal of one-kidney, one clip (1-K, 1C) hypertension by removal of the renal artery clip is accompanied by increased renal and vascular prostaglandin (PG) production. It was postulated that PG biosynthesis is stimulated in the unclipped hypertensive kidney. In order to test this hypothesis, we compared urinary excretion of PGE2 and 6-keto-PGF1 alpha (a breakdown product of PGI2) in perfused kidneys isolated from 1-K, 1C hypertensive rats, 1-K, sham-clipped rats and 1-K, 1C rats which had failed to become hypertensive. Urine was collected over 15 min periods at perfusion pressures of 100, 150 and 200 mmHg. At perfusion pressures of 100 and 150 mmHg there was no significant difference in PGE2 excretion between the three groups. In contrast, 6-keto-PGF1 alpha excretion at 150 mmHg was higher in the hypertensive rats compared with the sham-clipped (P less than 0.05) and failed hypertensive (P less than 0.01) rats. At 200 mmHg, both PGE2 and 6-keto-PGF1 alpha were significantly higher in the hypertensive rats than in the control groups. These increases in PG excretion were clearly dissociated from changes in urinary flow rates. The findings support the hypothesis of increased synthesis of renal vasodilatory and natriuretic PGs in 1-K, 1C hypertension which is particularly evident at higher perfusion pressures, such as may be encountered when the hypertensive kidney is unclipped and exposed to high arterial pressure.