Dexamethasone attenuates reversal of hypertension in one-kidney, one-clip rats.
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.
McGowan
H M
HM
Department of Medicine, University of Western Australia, Royal Perth Hospital.
Vandongen
R
R
Smith
B
B
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003404:Creatinine / Q000652:urine; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000652:urine; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012964:Sodium / Q000652:urine; D013929:Thromboxane B2 / Q000097:blood
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003907:Dexamethasone; D012964:Sodium; D003404:Creatinine; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D011188:Potassium