Spence C D, Coghlan J P, Denton D A, Mills E H, Whitworth J A, Scoggins B A
J Steroid Biochem. 1986 Sep;25(3):411-5. doi: 10.1016/0022-4731(86)90254-2.
This study investigated the effect of 5 day infusions of two structurally novel synthetic steroids, nivazol and cortivazol on blood pressure and in vivo indices of "glucocorticoid" and "mineralocorticoid" activity. Cortivazol at 24 mg/day raised mean arterial pressure (MAP) by 16 mmHg (P less than 0.001). This was associated with increased cardiac rate, and increased fasting plasma [glucose], polyuria and polydipsia a trilogy characteristic of glucocorticoid effect. Cortivazol had no consistent action on plasma [Na] or [K], but caused an initial transient urinary Na retention and raised urinary excretion of Na and K on days 3 and 4 of treatment. Nivazol at 24 mg/day raised MAP 10 mmHg (P less than 0.001), but cardiac rate was unchanged. This infusion was also associated with the glucocorticoid effects of increased fasting plasma [glucose] and increased urine volume. Plasma [K] fell from a control of 4.4 +/- 0.1 to 4.0 +/- 0.1 mmol/l (P less than 0.01) after 5 days of infusion. There was no significant effect of nivazol on urinary Na or K excretion. This study demonstrates that replacement of the 3-keto group, by a bulky phenylpyrazolo group fused to the A ring at position 2 and 3, does not diminish either pressor or glucocorticoid activity of steroids containing the typical 4-pregnene-3,20-dione nucleus and confirms that the 3 keto group is not essential for optimal glucocorticoid activity. It is the first demonstration of the pressor effect of these novel steroids.
本研究调查了两种结构新颖的合成类固醇（尼伐唑和可的伐唑）连续5天输注对血压以及“糖皮质激素”和“盐皮质激素”活性的体内指标的影响。可的伐唑剂量为24毫克/天，可使平均动脉压（MAP）升高16毫米汞柱（P<0.001）。这与心率加快、空腹血浆[葡萄糖]升高、多尿和烦渴有关，这是糖皮质激素作用的三联征。可的伐唑对血浆[钠]或[钾]没有一致的作用，但在治疗的第3天和第4天导致初始短暂的尿钠潴留，并增加钠和钾的尿排泄量。尼伐唑剂量为24毫克/天，使MAP升高10毫米汞柱（P<0.001），但心率未改变。这种输注还与空腹血浆[葡萄糖]升高和尿量增加的糖皮质激素作用有关。输注5天后，血浆[钾]从对照值4.4±0.1毫摩尔/升降至4.0±0.1毫摩尔/升（P<0.01）。尼伐唑对尿钠或钾排泄没有显著影响。本研究表明，在2和3位与A环稠合的庞大苯基吡唑基团取代3-酮基，不会降低含有典型4-孕烯-3,20-二酮核的类固醇的升压或糖皮质激素活性，并证实3-酮基对于最佳糖皮质激素活性不是必需的。这是这些新型类固醇升压作用的首次证明。
