This study examines the effect of dexamethasone (Dex), a phospholipase A2 inhibitor, on the reversal of 1-kidney, 1-clip (1K,1C) hypertension and the synthesis of phospholipase A2-dependent products. Male Sprague-Dawley 1K,1C hypertensive rats [blood pressure (BP) greater than 190 mmHg] were allocated to three groups: two groups were given daily oral doses of Dex (0.142 mg/kg in water) for 72 h, whereas the third group was given water only (controls). One of the Dex-treated groups was then sham unclipped (n = 9), while the other Dex-treated group (n = 8) and the control group (n = 8) were unclipped. Dex attenuated the BP fall in the unclipped (223 +/- 8-148 +/- 9 mmHg) compared with the control unclipped (226 +/- 9-114 +/- 5 mmHg) animals (P less than 0.005). Aortic 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) was reduced in unclipped Dex-treated rats (13.4 +/- 1.2 ng/mg) compared with unclipped control rats (16.3 +/- 1.4 ng/mg; P less than 0.05) but was higher than in the sham-unclipped Dex group (11.5 +/- 1.2 ng/mg; P less than 0.05). Serum thromboxane B2 (TxB2) in the unclipped Dex-treated group was lower than in the unclipped control rats (P less than 0.05) but higher than in sham-unclipped rats (P less than 0.05). Dex significantly increased urinary prostaglandin E2 (PGE2) excretion, whereas urinary 6-keto-PGF1 alpha was unaltered. After unclipping, both urinary PGE2 and 6-keto-PGF1 alpha increased significantly, although there was no obvious difference between Dex-treated and control animals. These findings demonstrate opposite effects of Dex on renal compared with extrarenal prostanoid synthesis and support the hypothesis that attenuation of aortic 6-keto-PGF1 alpha synthesis may be responsible for the smaller fall in BP after unclipping in Dex-treated rats.
Prostanoid synthesis by cultured intestinal epithelial and mononuclear cells in inflammatory bowel disease.