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高血压所致靶器官损害的机制:治疗潜力

Mechanisms of target organ damage caused by hypertension: therapeutic potential.

作者信息

Cohuet G, Struijker-Boudier H

机构信息

Cardiovascular Research Institute of Maastricht, Pharmacology and Toxicology, Universiteitssingel 50, PO BOX 616, 6200 MD Maastricht, The Netherlands.

出版信息

Pharmacol Ther. 2006 Jul;111(1):81-98. doi: 10.1016/j.pharmthera.2005.09.002. Epub 2005 Nov 8.

Abstract

Hypertension is a major risk factor for cardiovascular mortality and morbidity through its effects on target organs like the brain, heart, and kidney. Structural alterations in the microcirculation form a major link between hypertension and target organ damage. In this review, we describe damages related to hypertension in these target organs and the mechanisms involved in the pathogenesis of hypertension-induced cardiovascular diseases such as dementia, cardiac ischemia and remodeling, or nephropathy. We also focus on the therapeutical potential on the basis of such mechanisms. Several antihypertensive agents like diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin II (Ang II) receptor antagonists, beta-blockers, or calcium channel blockers (CCBs) have been shown to reduce effectively hypertension associated cardiovascular events and to improve end organ damage. More recently, aldosterone antagonism has also shown beneficial effects. Part of the favorable effects of these agents is due to blood pressure lowering as such. Other mechanisms such as oxidative stress, inflammation, or endothelial dysfunction have appeared to play a key role in the pathogenesis of target organ damage and therefore represent another important pathway for therapy. In this review, we discuss the different therapeutic approaches aiming at reducing cardiovascular events and damages induced by hypertension.

摘要

高血压通过对大脑、心脏和肾脏等靶器官的影响,成为心血管疾病死亡率和发病率的主要危险因素。微循环的结构改变是高血压与靶器官损害之间的主要联系。在本综述中,我们描述了这些靶器官中与高血压相关的损害,以及高血压诱导的心血管疾病(如痴呆、心脏缺血和重塑或肾病)发病机制中涉及的机制。我们还基于这些机制关注治疗潜力。利尿剂、血管紧张素转换酶(ACE)抑制剂、血管紧张素II(Ang II)受体拮抗剂、β受体阻滞剂或钙通道阻滞剂(CCB)等几种抗高血压药物已被证明能有效降低与高血压相关的心血管事件,并改善终末器官损害。最近,醛固酮拮抗作用也显示出有益效果。这些药物的部分有益作用归因于血压降低本身。氧化应激、炎症或内皮功能障碍等其他机制似乎在靶器官损害的发病机制中起关键作用,因此代表了另一条重要的治疗途径。在本综述中,我们讨论了旨在减少高血压引起的心血管事件和损害的不同治疗方法。

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