Coghlan J P, Denton D A, Mills E H, Nelson M A, Spence C D, Whitworth J A, Scoggins B A
Life Sci. 1984 Dec 24;35(26):2609-12. doi: 10.1016/0024-3205(84)90028-6.
We have previously reported that adrenocortical steroids raise blood pressure by a 'hypertensinogenic' mechanism of action which is not simply related to their classical 'mineralocorticoid' or 'glucocorticoid' actions. This study presents evidence for specific antagonism of this 'hypertensinogenic' activity. The effects of separate IV infusions of prednisolone (P) 100 mg/d and 9 alpha-fluoro-prednisolone (9 alpha F-P) 0.6 mg/d on mean arterial pressure (MAP), plasma [K], plasma [glucose] and urinary Na excretion (UNaV) after 2 days were studied in sheep. In the same group of sheep which received P alone for 2 days, 9 alpha F-P was given for a further 2 days while continuing the P infusion (P + 9 alpha F-P). P alone had no effect on MAP or plasma [K] or UNaV but increased plasma [glucose], effects which are characteristic of 'glucocorticoid' activity. 9 alpha F-P alone increased MAP by 14 mmHg (P less than 0.001) and reduced plasma [K] and UNaV but had no effect on plasma [glucose]. Thus 9 alpha F-P exhibited both 'hypertensionogenic' and 'mineralocorticoid' activity. In the sheep which received the combined P + 9 alpha F-P infusion, the increase in MAP normally produced by 9 alpha F-P was blocked. Although pretreatment with P blocked the pressor effect of 9 alpha F-P, it did not alter the 'mineralocorticoid' effects, namely hypokalaemia and urinary Na retention, produced when 9 alpha F-P was infused alone. These results provide further evidence for our concept of a 'hypertensinogenic' class of steroid activity and are the first demonstration of specific antagonism of steroid induced hypertension.
我们之前曾报道，肾上腺皮质类固醇通过一种“致高血压”作用机制升高血压，这一机制并非简单地与其经典的“盐皮质激素”或“糖皮质激素”作用相关。本研究提供了针对这种“致高血压”活性的特异性拮抗作用的证据。在绵羊中研究了分别静脉输注100mg/d泼尼松龙（P）和0.6mg/d 9α-氟泼尼松龙（9αF-P）2天后对平均动脉压（MAP）、血浆[钾]、血浆[葡萄糖]和尿钠排泄（UNaV）的影响。在同一组单独接受P 2天的绵羊中，在继续输注P（P + 9αF-P）的同时，再给予9αF-P 2天。单独使用P对MAP、血浆[钾]或UNaV无影响，但增加了血浆[葡萄糖]，这些是“糖皮质激素”活性的特征性效应。单独使用9αF-P使MAP升高14mmHg（P＜0.001），降低了血浆[钾]和UNaV，但对血浆[葡萄糖]无影响。因此，9αF-P表现出“致高血压”和“盐皮质激素”活性。在接受P + 9αF-P联合输注的绵羊中，9αF-P通常引起的MAP升高被阻断。尽管用P预处理可阻断9αF-P的升压作用，但并未改变单独输注9αF-P时产生的“盐皮质激素”效应，即低钾血症和尿钠潴留。这些结果为我们关于“致高血压”类类固醇活性的概念提供了进一步的证据，并且是类固醇诱导的高血压特异性拮抗作用的首次证明。
