Goto A, Yamada K, Hazama H, Uehara Y, Atarashi K, Hirata Y, Kimura K, Omata M
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Hypertension. 1996 Sep;28(3):421-5. doi: 10.1161/01.hyp.28.3.421.
Molecular mechanisms related to sodium retention have been implicated in the pathogenesis of hypertension. It is unclear how sodium retention leads to a rise in blood pressure, but ouabainlike compound may act as a final common pathway in sodium-induced hypertension. In ectopic corticotropin syndrome, hypertension has been attributed to cortisol inactivation overload, giving rise to mineralocorticoid-type hypertension. We sequentially measured plasma and urinary levels of ouabainlike compound over 2 months to evaluate its role in the hypertensive mechanisms in a 64-year-old man with this syndrome caused by lung cancer. His data included hypokalemia and increased cortisol concentrations, corticotropin levels, and urinary 17-hydroxycorticosteroid excretion. Plasma renin activity was suppressed. Plasma and urinary levels of ouabainlike compound were markedly increased concomitantly with high blood pressure. The maximum plasma level was 40-fold the normal range of the subject. After chemotherapy, ouabainlike compound levels gradually decreased in parallel with the decline in blood pressure and rise in potassium concentration. A correlation was observed between plasma and urinary levels of ouabainlike compound (P < .05). Plasma and urinary levels of ouabainlike compound correlated with systolic (P < .01) and diastolic (P < .05) pressures, respectively. The peak of ouabainlike compound in plasma and urine coincided with that of authentic ouabain on high-performance liquid chromatography. Ouabainlike compound derived from urine inhibited [3H]ouabain binding to human erythrocytes. These findings suggest that ouabainlike compound with biological activity could partly account for hypertension in ectopic corticotropin syndrome.
与钠潴留相关的分子机制已被认为与高血压的发病机制有关。目前尚不清楚钠潴留如何导致血压升高，但类哇巴因化合物可能是钠诱导性高血压的最终共同途径。在异位促肾上腺皮质激素综合征中，高血压被认为是由于皮质醇失活负荷过重，从而引发盐皮质激素型高血压。我们连续2个月测量了一名64岁患有由肺癌引起的该综合征男性患者的血浆和尿液中类哇巴因化合物的水平，以评估其在高血压机制中的作用。他的数据包括低钾血症以及皮质醇浓度、促肾上腺皮质激素水平和尿17-羟皮质类固醇排泄增加。血浆肾素活性受到抑制。类哇巴因化合物的血浆和尿液水平与高血压同时显著升高。血浆最高水平是该受试者正常范围的40倍。化疗后，类哇巴因化合物水平随着血压下降和钾浓度升高而逐渐降低。观察到类哇巴因化合物的血浆和尿液水平之间存在相关性（P < .05）。类哇巴因化合物的血浆和尿液水平分别与收缩压（P < .01）和舒张压（P < .05）相关。血浆和尿液中类哇巴因化合物的峰值与高效液相色谱上纯哇巴因的峰值一致。源自尿液的类哇巴因化合物抑制[3H]哇巴因与人红细胞的结合。这些发现表明具有生物活性的类哇巴因化合物可能部分解释了异位促肾上腺皮质激素综合征中的高血压。
