McGowan H M, Vandongen R, Smith B
Department of Medicine, University of Western Australia, Royal Perth Hospital.
Am J Physiol. 1988 Oct;255(4 Pt 2):H717-21. doi: 10.1152/ajpheart.1988.255.4.H717.
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.
本研究考察了磷脂酶A2抑制剂地塞米松（Dex）对1肾1夹（1K，1C）高血压逆转及磷脂酶A2依赖性产物合成的影响。将雄性Sprague-Dawley 1K，1C高血压大鼠[血压（BP）大于190 mmHg]分为三组：两组每日口服Dex（0.142 mg/kg溶于水中），持续72小时，而第三组仅给予水（对照组）。然后，其中一组接受Dex治疗的大鼠进行假去夹术（n = 9），而另一组接受Dex治疗的大鼠（n = 8）和对照组（n = 8）进行去夹术。与未去夹的对照动物（226±9 - 114±5 mmHg）相比，Dex减轻了去夹大鼠的血压下降（223±8 - 148±9 mmHg）（P < 0.005）。与未去夹的对照大鼠（16.3±1.4 ng/mg；P < 0.05）相比，去夹的Dex治疗大鼠主动脉6-酮前列腺素F1α（6-酮-PGF1α）降低（13.4±1.2 ng/mg），但高于假去夹的Dex组（11.5±1.2 ng/mg；P < 0.05）。去夹的Dex治疗组血清血栓素B2（TxB2）低于未去夹的对照大鼠（P < 0.05），但高于假去夹大鼠（P < 0.05）。Dex显著增加尿前列腺素E2（PGE2）排泄，而尿6-酮-PGF1α未改变。去夹后，尿PGE2和6-酮-PGF1α均显著增加，尽管Dex治疗组和对照组动物之间没有明显差异。这些发现表明，与肾外前列腺素合成相比，Dex对肾脏的作用相反，并支持以下假设：主动脉6-酮-PGF1α合成的减弱可能是Dex治疗大鼠去夹后血压下降较小的原因。
