Walker B R, Best R, Shackleton C H, Padfield P L, Edwards C R
Department of Medicine, Western General Hospital, University of Edinburgh, Scotland, UK.
Hypertension. 1996 Feb;27(2):190-6. doi: 10.1161/01.hyp.27.2.190.
Glucocorticoids raise blood pressure but were thought not to play a pathophysiological role in essential hypertension when it was demonstrated that cortisol secretion rates and circulating concentrations are normal in this disease. However, recent observations suggest that increased tissue sensitivity to cortisol, mediated by either abnormal glucocorticoid receptors or impaired inactivation of cortisol by 11 beta-dehydrogenase, may allow cortisol to raise blood pressure despite normal circulating concentrations. We studied 11 patients with essential hypertension and 11 matched normotensive control subjects. Dermal vasoconstriction after topical application of both cortisol (16 +/- 4 versus 32 +/- 5 U, control subjects versus hypertensive patients; P < .02) and beclomethasone dipropionate (75 +/- 10 versus 100 +/- 7 U; P < .05) was increased in the hypertensive patients. Hypothalamic-pituitary glucocorticoid receptor sensitivity was normal, as judged by basal cortisol secretion rates and suppression of plasma cortisol during sequential overnight dexamethasone suppression tests. 11 beta-Dehydrogenase activity was impaired in essential hypertension, as judged by prolonged half-lives of [11 alpha-3H]cortisol (44 +/- 4 versus 58 +/- 4 minutes, control subjects versus hypertensive patients; P < .02). However, this did not correlate with the dermal vasoconstrictor response. We conclude that vasoconstrictor sensitivity to glucocorticoids is increased in essential hypertension and that this may initiate and/or sustain the increased peripheral vascular resistance that characterizes this disease. The mechanism of increased sensitivity remains uncertain, but it will be important to establish whether it relates to genetic abnormalities of the glucocorticoid receptor that have been observed in animal models and young individuals who are predisposed to essential hypertension.
糖皮质激素会升高血压，但当有研究表明在原发性高血压患者中皮质醇分泌率和循环浓度正常时，人们曾认为它在原发性高血压的病理生理过程中不起作用。然而，最近的观察结果表明，由异常的糖皮质激素受体或11β-脱氢酶对皮质醇的失活受损介导的组织对皮质醇敏感性增加，可能使皮质醇在循环浓度正常的情况下仍能升高血压。我们研究了11例原发性高血压患者和11例匹配的血压正常的对照者。原发性高血压患者在局部应用皮质醇（对照者与高血压患者分别为16±4与32±5单位；P<0.02）和二丙酸倍氯米松（75±10与100±7单位；P<0.05）后皮肤血管收缩增强。根据基础皮质醇分泌率以及在连续过夜地塞米松抑制试验期间血浆皮质醇的抑制情况判断，下丘脑-垂体糖皮质激素受体敏感性正常。根据[11α-3H]皮质醇的半衰期延长判断，原发性高血压患者的11β-脱氢酶活性受损（对照者与高血压患者分别为44±4与58±4分钟；P<0.02）。然而，这与皮肤血管收缩反应并无相关性。我们得出结论，原发性高血压患者对糖皮质激素的血管收缩敏感性增加，这可能引发和/或维持了该病特征性的外周血管阻力增加。敏感性增加的机制仍不确定，但确定它是否与动物模型和易患原发性高血压的年轻个体中观察到的糖皮质激素受体基因异常有关将很重要。
