Sennett J A, Brown R D, Island D P, Yarbro L R, Watson J T, Slaton P E, Hollifield J W, Liddle G W
Circ Res. 1975 Jun;36(6 Suppl 1):2-9. doi: 10.1161/01.res.36.6.2.
Patients with low-renin essential hypertension have certain features consistent with excessive mineralocorticoid activity. Because known mineralocorticoids are normal in the majority of low-renin essential hypertension patients, an unknown mineralocorticoid was sought in the urine of such patients. Urine extracts from patients with low-renin essential hypertension were assayed for mineralocorticoid activity in adrenalectomized rats and found to contain more such activity than could be accounted for by the known mineralocorticoids in the extracts. The factor responsible for the unexplained mineralocorticoid activity was purfied and then identified by mass spectral analysis as 16beta-hydroxydehydroepiandrosterone (16beta-OH-DHEA). Synthetic 16beta-OH-DHEA was found to have a mineralocorticoid potency one-fortieth that of aldosterone in the rat bioassay. The mineralocorticoid effects of both the urine extracts and the synthetic steroid were blocked in the rat by spironolactone, a mineralocorticoid antagonist. A specific assay for 16beta-OH-DHEA was developed, and its level in the urine was found to be elevated in patients with low-renin essential hypertension.
低肾素性原发性高血压患者具有某些与盐皮质激素活性过高相符的特征。由于大多数低肾素性原发性高血压患者体内已知的盐皮质激素水平正常，因此在这类患者的尿液中寻找一种未知的盐皮质激素。对低肾素性原发性高血压患者的尿液提取物在肾上腺切除的大鼠中进行盐皮质激素活性检测，发现其所含的这种活性比提取物中已知盐皮质激素所能解释的活性更多。对导致无法解释的盐皮质激素活性的因子进行纯化，然后通过质谱分析鉴定为16β - 羟基脱氢表雄酮（16β - OH - DHEA）。在大鼠生物测定中，发现合成的16β - OH - DHEA的盐皮质激素效力是醛固酮的四十分之一。盐皮质激素拮抗剂螺内酯可阻断大鼠尿液提取物和合成类固醇的盐皮质激素作用。开发了一种针对16β - OH - DHEA的特异性检测方法，发现低肾素性原发性高血压患者尿液中该物质的水平升高。
