Funder John W
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Am J Cardiovasc Drugs. 2007;7(3):151-7. doi: 10.2165/00129784-200707030-00001.
The roles of aldosterone and mineralocorticoid receptors in cardiovascular disease have been expanded, refined, and distinguished over the past decade. Primary aldosteronism has been shown to represent 8-13% (rather than <1%) of unselected hypertensive patients, and patients with primary aldosteronism to have higher indices of cardiovascular damage than controls of the same age, sex, and BP status. While this represents a clearly expanded role for aldosterone, it is improbable that the hormone (as opposed to the mineralocorticoid receptor) plays a major role in other instances of essential hypertension, in cardiac failure, or in atherosclerosis. Evidence from studies in these conditions supports a substantial role for mineralocorticoid receptor activation; low baseline aldosterone levels, and evidence from experimental in vivo studies, support a role for normal levels of physiologic glucocorticoids in activating mineralocorticoid receptors (MR) in the context of tissue damage and reactive oxygen species generation. These relatively recent insights suggest the potential therapeutic role for MR antagonists across a spectrum of cardiovascular disease, as vascular protectants even when circulating levels of aldosterone are low.
在过去十年中,醛固酮和盐皮质激素受体在心血管疾病中的作用得到了扩展、细化和区分。原发性醛固酮增多症已被证明在未经选择的高血压患者中占8%-13%(而非<1%),且原发性醛固酮增多症患者的心血管损伤指标高于相同年龄、性别和血压状态的对照组。虽然这表明醛固酮的作用明显扩大,但在原发性高血压的其他病例、心力衰竭或动脉粥样硬化中,该激素(与盐皮质激素受体相对)发挥主要作用的可能性不大。这些病症的研究证据支持盐皮质激素受体激活起重要作用;低基线醛固酮水平以及体内实验研究的证据支持在组织损伤和活性氧生成的情况下,生理糖皮质激素的正常水平在激活盐皮质激素受体(MR)中发挥作用。这些相对较新的见解表明,MR拮抗剂在一系列心血管疾病中具有潜在的治疗作用,即使醛固酮的循环水平较低时,也可作为血管保护剂。