Section of Nephrology, Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, PO Box 208064, New Haven, CT 06520, USA.
Pediatr Nephrol. 2012 Jul;27(7):1059-66. doi: 10.1007/s00467-011-1928-4. Epub 2011 Jul 9.
Glucocorticoid-induced hypertension is a common clinical problem that is poorly understood, thus rendering treatment strategies sub-optimal. This form of hypertension has been commonly thought to be mediated by excess sodium and water reabsorption by the renal mineralocorticoid receptor. However, experimental and clinical data in both humans and animal models suggest important roles for the glucocorticoid receptor as well, in both the pathogenesis and maintenance of this hypertension. The glucocorticoid receptor is widely expressed in a number of organ systems relevant to blood pressure regulation, including the kidney, the brain and the vasculature. In vitro studies in isolated kidney tissues as well as in vascular smooth muscle and vascular endothelial cells have attempted to elucidate the molecular physiology of glucocorticoid-induced hypertension, but have generally been limited by the inability to study signaling pathways in an intact organism. More recently, the power of mouse genetics has been employed to examine the tissue-specific contributions of vascular and extra-vascular tissues to this form of hypertension. Here we review recent developments in our understanding of the pathogenesis of glucocorticoid-induced hypertension.
糖皮质激素诱导的高血压是一种常见的临床问题，但人们对此了解甚少，因此治疗策略并不理想。这种高血压通常被认为是由肾脏盐皮质激素受体过度吸收钠和水引起的。然而，人类和动物模型中的实验和临床数据表明，糖皮质激素受体在这种高血压的发病机制和维持中也起着重要作用。糖皮质激素受体在许多与血压调节相关的器官系统中广泛表达，包括肾脏、大脑和血管。在离体肾脏组织以及血管平滑肌和血管内皮细胞中的体外研究试图阐明糖皮质激素诱导的高血压的分子生理学，但由于无法在完整的生物体中研究信号通路，这些研究通常受到限制。最近，小鼠遗传学的强大功能被用于研究血管和血管外组织对这种高血压的组织特异性贡献。在这里，我们回顾了对糖皮质激素诱导的高血压发病机制的理解的最新进展。
