Cardiovascular Research Center, Landspitali the University Hospital of Iceland, IS-101, Reykjavik, Iceland,
Curr Hypertens Rep. 2013 Oct;15(5):484-8. doi: 10.1007/s11906-013-0379-7.
Hypertension is an established risk factor for stroke, premature coronary artery disease and heart failure. Control of elevated blood pressure has been shown to result in significant reduction of cardiovascular risk. Aldosterone, the final product of the renin-angiotensin-aldosterone system (RAAS), not only causes salt and water reabsorbtion in the kidneys through its effect on the mineralocorticoid hormone receptor (MR), but also an MR-independent effect, not regulated by conventional MR blockade. Although many pharmacological agents target different levels of the RAAS cascade, these generally result in elevated renin concentration and plasma renin activity. This upstream feedback response subsequently results in elevated levels of angiotensin II, a potent vasoconstrictor and stimulus to aldosterone release. This aldosterone breakthrough counteracts the long-term blood pressure-lowering effect of these agents. Therefore the development of a new class of pharmacologic agents that directly inhibit the production of aldosterone may prove clinically useful in reducing aldosterone and thereby controlling elevated blood pressure.
高血压是中风、过早冠心病和心力衰竭的既定危险因素。已证实，控制血压升高可显著降低心血管风险。醛固酮是肾素-血管紧张素-醛固酮系统（RAAS）的终产物，不仅通过其对盐皮质激素受体（MR）的作用导致肾脏中盐和水的再吸收，而且还具有不受常规 MR 阻断调节的 MR 非依赖性作用。尽管许多药理药物针对 RAAS 级联的不同水平，但这些药物通常会导致肾素浓度和血浆肾素活性升高。这种上游反馈反应随后导致血管紧张素 II 水平升高，血管紧张素 II 是一种有效的血管收缩剂和醛固酮释放的刺激物。这种醛固酮突破抵消了这些药物的长期降压作用。因此，开发一类直接抑制醛固酮产生的新型药物可能在降低醛固酮和控制血压升高方面具有临床应用价值。
