Montrella-Waybill M, Clore J N, Schoolwerth A C, Watlington C O
Department of Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0145.
J Clin Endocrinol Metab. 1991 May;72(5):1060-6. doi: 10.1210/jcem-72-5-1060.
We have previously shown that high dose cortisol (F; 240 mg/day)-induced Na+ retention and systolic blood pressure (BP) increases are not inhibited by the glucocorticoid (type II) receptor antagonist RU486. Adequacy of type II receptor blockade with RU486 was clearly demonstrated, indicating that the Na+ retention was not mediated through the glucocorticoid receptor. Spironolactone (Sp: 400 mg/day), in a preliminary assessment, also did not inhibit F-induced Na+ retention. The purpose of this study was to determine whether the Na+ retention produced by F administration is mediated by the type I receptor by comparing the effects of F to a potent type I agonist [9 alpha-fludrohydrocortisone (9 alpha FF)] with and without Sp administration. The effects of the two agonists and Sp on urinary K excretion and BP were also compared. Normal male volunteers, on a constant daily diet for 10 days, received either F (240 mg/day) or 9 alpha FF (3.0 mg/day) with or without Sp (400 mg/day) for the last 5 days. The mean cumulative reductions in Na+ excretion during the 5 days compared to baseline values before hormone administration were 255 +/- 38 and 494 +/- 81 mmol/5 days for F (n = 9) and 9 alpha FF (n = 5), respectively (P = 0.01). Sp (n = 5) completely inhibited 9 alpha FF-induced Na+ retention (494 +/- 81 vs. -37 +/- 130 mmol/5 days; P less than 0.01), but had no effect (n = 5) on F-induced Na+ retention (255 +/- 38 vs. 193 +/- 50 mmol/5 days; P = NS). After the expected first day kaliuresis, the effects of both steroids on net cumulative urinary K+ excretion were minimal. Systolic BP was increased by F, but not 9 alpha FF, and Sp did not inhibit this increase. A 2-fold greater Sp-inhibitable Na(+)-retaining effect of the mineralocorticoid demonstrates that the failure of Sp to block F-induced Na+ retention is not due to inadequate type I receptor blockade. Based on these findings and earlier studies, we conclude that high dose (stress level) F-induced Na+ retention and systolic BP increase are not mediated by either the mineralo- or glucocorticoid receptor in normal man.
我们之前已经表明，高剂量皮质醇（F；240毫克/天）诱导的钠潴留和收缩压（BP）升高不受糖皮质激素（II型）受体拮抗剂RU486的抑制。RU486对II型受体的阻断作用充分得到证实，这表明钠潴留并非通过糖皮质激素受体介导。在初步评估中，螺内酯（Sp：400毫克/天）也未抑制F诱导的钠潴留。本研究的目的是通过比较F与一种强效I型激动剂[9α-氟氢可的松（9αFF）]在给予和未给予Sp时的作用，来确定F给药产生的钠潴留是否由I型受体介导。还比较了这两种激动剂和Sp对尿钾排泄和血压的影响。正常男性志愿者在连续10天保持恒定日常饮食的情况下，在最后5天接受F（240毫克/天）或9αFF（3.0毫克/天），同时给予或不给予Sp（400毫克/天）。与激素给药前的基线值相比，F组（n = 9）和9αFF组（n = 5）在这5天内钠排泄的平均累积减少量分别为255±38和494±81毫摩尔/5天（P = 0.01）。Sp组（n = 5）完全抑制了9αFF诱导的钠潴留（494±81对-37±130毫摩尔/5天；P＜0.01），但对F诱导的钠潴留无影响（n = 5）（255±38对193±50毫摩尔/5天；P = 无显著性差异）。在预期的第一天钾利尿之后，两种类固醇对净累积尿钾排泄的影响都很小。F使收缩压升高，但9αFF未使其升高，并且Sp并未抑制这种升高。盐皮质激素的Sp可抑制的钠潴留作用大2倍，这表明Sp未能阻断F诱导的钠潴留并非由于I型受体阻断不足。基于这些发现和早期研究，我们得出结论，高剂量（应激水平）F诱导的钠潴留和收缩压升高在正常男性中并非由盐皮质激素或糖皮质激素受体介导。
