Whitworth J A, Gordon D, Andrews J, Scoggins B A
Department of Nephrology, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
J Hypertens. 1989 Jul;7(7):537-49. doi: 10.1097/00004872-198907000-00005.
In previous studies, administration of adrenocorticotrophin (ACTH; 0.5 mg i.m. b.d. for 5 days) to normal subjects produced an adrenally dependent rise in blood pressure (BP) of some 20 mmHg, accompanied by an increase in cardiac output and an increase in plasma volume. The BP and metabolic effects of ACTH (increase in plasma glucose, fall in eosinophils, increase in body weight and urine sodium retention) were reproduced by infusion of the glucocorticoid (GC) cortisol at rates (6-8 mg/h) which reproduced the blood concentrations of the steroid achieved with ACTH administration. Oral administration (hydrocortisone 200 mg daily) produced similar changes qualitatively, although the cortisol concentrations and increase in pressure (12 mmHg) were less. Plasma volume was increased. To determine the role of urine sodium retention and plasma volume expansion in the hypertension, we gave synthetic steroids to six normal subjects for 5 days, at doses which were calculated to be similar for GC activity, but which had little or no mineralocorticoid (MC) activity. Prednisolone (40 mg/day), methylprednisolone (32 mg/day), triamcinolone (40 mg/day) and dexamethasone (8 mg/day) all produced equivalent GC effects (increase in plasma glucose, increase in total white cell count, fall in direct eosinophil count). There were no MC effects with any of the steroids. Body weight did not increase and urinary sodium excretion increased rather than decreased. Plasma volume (125I human serum albumin) and haematocrit were unchanged. BP rose with all four steroids: systolic BP rose by 13 mmHg with prednisolone, by 9 mmHg with methylprednisolone, by 10 mmHg with triamcinolone, and by 6 mmHg with dexamethasone. Diastolic BP increases were 8, 11, 8 and 7 mmHg, respectively. Thus, neither MC activity nor an increase in plasma volume is essential for steroids to induce an increase in blood pressure. Therefore, screening of synthetic GCs to minimize MC activity will not prevent hypertensive complications.
在以往的研究中，给正常受试者注射促肾上腺皮质激素（ACTH；0.5毫克，肌肉注射，每日两次，共5天）会使血压（BP）依赖肾上腺升高约20毫米汞柱，同时心输出量增加，血浆容量增加。ACTH的血压和代谢效应（血浆葡萄糖增加、嗜酸性粒细胞减少、体重增加和尿钠潴留）可通过以一定速率（6 - 8毫克/小时）输注糖皮质激素（GC）皮质醇来重现，该速率可使类固醇的血药浓度达到注射ACTH时的水平。口服给药（氢化可的松每日200毫克）在性质上产生了类似的变化，尽管皮质醇浓度和血压升高幅度（12毫米汞柱）较小。血浆容量增加。为了确定尿钠潴留和血浆容量扩张在高血压中的作用，我们给6名正常受试者服用合成类固醇5天，剂量经计算具有相似的GC活性，但几乎没有或没有盐皮质激素（MC）活性。泼尼松龙（40毫克/天）、甲泼尼龙（32毫克/天）、曲安西龙（40毫克/天）和地塞米松（8毫克/天）均产生了等效的GC效应（血浆葡萄糖增加、白细胞总数增加、直接嗜酸性粒细胞计数减少）。这些类固醇均无MC效应。体重未增加，尿钠排泄增加而非减少。血浆容量（125I人血清白蛋白）和血细胞比容未改变。使用这四种类固醇血压均升高：泼尼松龙使收缩压升高13毫米汞柱，甲泼尼龙使收缩压升高9毫米汞柱，曲安西龙使收缩压升高10毫米汞柱，地塞米松使收缩压升高6毫米汞柱。舒张压升高分别为8、11、8和7毫米汞柱。因此，MC活性和血浆容量增加对于类固醇诱导血压升高都不是必需的。所以，筛选合成GC以尽量减少MC活性并不能预防高血压并发症。
