Hui R T, Grose J H, Lebel M, Falardeau P
Laboratory on Prostaglandins, Université de Montréal, Québec, Canada.
Hypertension. 1990 Feb;15(2):198-203. doi: 10.1161/01.hyp.15.2.198.
The goal of this study was to determine the role of prostanoids in a new model of mineralocorticoid-dependent hypertension induced by the subcutaneous infusion of aldosterone (1 micrograms/hr) to normal male Sprague-Dawley rats. This regimen caused a mild and gradual increase in systolic pressure over a period of 4 weeks (113 +/- 1 vs. 137 +/- 3 mm Hg) and was associated with an increase in the in vivo formation of prostaglandins I2 and E2 and of thromboxane A2 in the kidney. High sodium intake induced a fall in the urinary levels of prostaglandin E2 and a rise in the arterial pressure of control rats (126 +/- 1 vs. 113 +/- 1 mm Hg) but did not influence aldosterone-induced hypertension. Indomethacin (3.0 mg/kg/day) caused a profound inhibition of the in vivo synthesis of prostaglandin I2 and thromboxane A2 without modifying the renal production of prostaglandin E2. Although indomethacin exerted no effect on aldosterone-induced hypertension in rats fed a normal diet, it caused a further rise in systolic pressure in aldosterone-treated rats fed a high sodium diet (157 +/- 6 vs. 140 +/- 4 mm Hg). The results of this study in a model of aldosterone-induced mild hypertension in the rat indicate that 1) aldosterone exerts a stimulatory effect on the renal synthesis of prostanoid, particularly prostaglandin E2; 2) thromboxane A2 and prostaglandin I2 do not seem to play a role in aldosterone-induced hypertension under conditions of normal dietary salt intake, whereas the role of prostaglandin E2 is unclear; 3) there is enough sodium in a normal diet to allow for the maximal expression of the hypertensive effect of aldosterone; 4) prostaglandin I2 seems to play a significant role in modulating the cardiovascular impact of a high sodium diet in aldosterone-treated rats; and 5) the renal biosynthesis of prostaglandin E2 is particularly resistant to the inhibitory effect of indomethacin in vivo.
本研究的目的是确定前列腺素类物质在一种新的盐皮质激素依赖性高血压模型中的作用，该模型通过向正常雄性斯普拉格-道利大鼠皮下输注醛固酮（1微克/小时）诱导而成。这种给药方案在4周时间内使收缩压轻度逐渐升高（113±1对137±3毫米汞柱），并与肾脏中前列腺素I2、E2以及血栓素A2的体内生成增加有关。高钠摄入导致对照大鼠尿中前列腺素E2水平下降以及动脉压升高（126±1对113±1毫米汞柱），但不影响醛固酮诱导的高血压。吲哚美辛（3.0毫克/千克/天）可显著抑制前列腺素I2和血栓素A2的体内合成，而不改变肾脏中前列腺素E2的生成。虽然吲哚美辛对正常饮食喂养的大鼠的醛固酮诱导的高血压没有影响，但它使高钠饮食喂养的醛固酮处理大鼠的收缩压进一步升高（157±6对140±4毫米汞柱）。本研究在大鼠醛固酮诱导的轻度高血压模型中的结果表明：1）醛固酮对肾脏前列腺素类物质的合成，特别是前列腺素E2的合成具有刺激作用；2）在正常饮食盐摄入条件下，血栓素A2和前列腺素I2似乎在醛固酮诱导的高血压中不起作用，而前列腺素E2的作用尚不清楚；3）正常饮食中有足够的钠，可使醛固酮的高血压作用得以最大程度表达；4）前列腺素I2似乎在调节高钠饮食对醛固酮处理大鼠的心血管影响方面起重要作用；5）前列腺素E2的肾脏生物合成在体内对吲哚美辛的抑制作用特别耐药。
