Dendorfer A, Dominiak P, Schunkert H
Medizinische Klinik II, Universitätsklinikum Schleswig-Hostein, Lübeck, Germany.
Handb Exp Pharmacol. 2005(170):407-42. doi: 10.1007/3-540-27661-0_15.
The biological actions of angiotensin II (ANG), the most prominent hormone of the renin-angiotensin-aldosterone system (RAAS), may promote the development of atherosclerosis in many ways. ANG aggravates hypertension, metabolic syndrome, and endothelial dysfunction, and thereby constitutes a major risk factor for cardiovascular disease. The formation of atherosclerotic lesions involves local uptake, synthesis and oxidation of lipids, inflammation, as well as cellular migration and proliferation--mechanisms that may all be enhanced by ANG via its AT1 receptor. ANG may also increase the risk of acute thrombosis by destabilizing atherosclerotic plaques and enhancing the activity of thrombocytes and coagulation. After myocardial infarction, ANG promotes myocardial remodeling and fibrosis, and its many pathological mechanisms deteriorate the prognosis of these high-risk patients in particular. Therapeutically, inhibitors of the angiotensin I-converting enzyme (ACEI) and AT1 receptor blockers (ARB) are available to suppress the generation and cellular signaling of ANG, respectively. Despite major differences in the efficacy of ANG suppression and the modulation of other hormones and receptors, both classes of drugs are generally effective in attenuating numerous pathomechanisms of ANG in vitro, and in diminishing the development of atherosclerotic lesions and restenosis after angioplasty in various animal models. In clinical therapy, ACEI and ACE are well-tolerated antihypertensive drugs that also improve the prognosis of heart failure patients. After myocardial infarction and in stable coronary heart disease, ACEI have been shown to reduce mortality in a manner independent of hemodynamic alterations. However, there is little evidence that inhibitors of the RAAS may be effective against arterial restenosis, and a possible benefit of these substances compared to other antihypertensive drugs in the primary prevention of coronary heart disease in hypertensive patients is still a matter of debate, possibly depending on the specific substance and condition being investigated. As such, the general clinical efficacy of ACEI and ARB may be due to a positive influence on hemodynamic load, vascular function, myocardial remodeling, and neuro-humoral regulation, rather than to a direct attenuation of the atherosclerotic process. Further therapeutic advances may be achieved by identifying optimum drugs, patient populations, and treatment protocols.
血管紧张素II（ANG）是肾素-血管紧张素-醛固酮系统（RAAS）中最主要的激素，其生物学作用可通过多种方式促进动脉粥样硬化的发展。ANG会加重高血压、代谢综合征和内皮功能障碍，从而构成心血管疾病的主要危险因素。动脉粥样硬化病变的形成涉及脂质的局部摄取、合成和氧化、炎症以及细胞迁移和增殖，而ANG可通过其AT1受体增强所有这些机制。ANG还可能通过使动脉粥样硬化斑块不稳定并增强血小板活性和凝血功能来增加急性血栓形成的风险。心肌梗死后，ANG会促进心肌重塑和纤维化，其众多病理机制尤其会使这些高危患者的预后恶化。在治疗方面，可分别使用血管紧张素I转换酶抑制剂（ACEI）和AT1受体阻滞剂（ARB）来抑制ANG的生成和细胞信号传导。尽管在抑制ANG的效果以及对其他激素和受体的调节方面存在重大差异，但这两类药物在体外通常都能有效减弱ANG的多种病理机制，并在各种动物模型中减少动脉粥样硬化病变的发展和血管成形术后的再狭窄。在临床治疗中，ACEI和ARB是耐受性良好的降压药物，也能改善心力衰竭患者的预后。在心肌梗死和稳定型冠心病患者中，ACEI已被证明可独立于血流动力学改变降低死亡率。然而，几乎没有证据表明RAAS抑制剂对动脉再狭窄有效，与其他降压药物相比，这些物质在高血压患者冠心病一级预防中的潜在益处仍存在争议，这可能取决于所研究的具体物质和病情。因此，ACEI和ARB的总体临床疗效可能归因于对血流动力学负荷、血管功能、心肌重塑和神经体液调节的积极影响，而非直接减弱动脉粥样硬化进程。通过确定最佳药物、患者群体和治疗方案，可能会取得进一步的治疗进展。
