Unger T, Culman J, Gohlke P
Institute of Pharmacology, University of Kiel, Germany.
J Hypertens Suppl. 1998 Sep;16(7):S3-9.
The renin-angiotensin system is a widely studied hormonal system that comprises substrate-enzyme interactions, the end result of which is the production of the active peptide angiotensin II. Because angiotensin II affects blood pressure control, sodium and water homeostasis, and cardiovascular function and structure, a great deal of research effort has been directed toward blocking the renin-angiotensin system. Angiotensin II also may be involved in end-organ damage in hypertension, heart failure, and vascular disease.
At least two subtypes of angiotensin II receptors have been identified, angiotensin type 1 (AT)1 and type 2 (AT2). The AT1 receptor mediates all the known actions of angiotensin II on blood pressure control. Additionally, research has indicated that the AT1 receptor modulates cardiac contractility and glomerular filtration, increases renal tubular sodium reabsorption, and cardiac and vascular hypertrophy. Less is known about the function of the AT2 receptor. Evidence suggests that the AT2 receptor inhibits cell proliferation and reverses the AT1-induced hypertrophy. Indeed, these receptors are thought to exert opposing effects.
This newly introduced class of drugs is able to inhibit the renin-angiotensin system at the receptor level by specifically blocking the AT1 receptor subtype. These drugs induce a dose-dependent blockade of angiotensin II effects, resulting in reduced blood pressure, urinary protein, and glomerular sclerosis. It is postulated that AT1 receptor antagonists may provide end-organ protection by blocking angiotensin II effects via the AT1 receptor, leaving the AT2 receptor unopposed. Consequently, these agents may reduce the morbidity and mortality that result from myocardial infarction and other conditions resulting from structural alterations in the heart, kidney, and vasculature.
肾素-血管紧张素系统是一个被广泛研究的激素系统，它包括底物-酶相互作用，其最终结果是产生活性肽血管紧张素II。由于血管紧张素II影响血压控制、钠和水平衡以及心血管功能和结构，大量的研究工作致力于阻断肾素-血管紧张素系统。血管紧张素II也可能参与高血压、心力衰竭和血管疾病中的终末器官损伤。
血管紧张素II受体：至少已鉴定出两种血管紧张素II受体亚型，即1型（AT）1和2型（AT2）。AT1受体介导血管紧张素II对血压控制的所有已知作用。此外，研究表明，AT1受体调节心脏收缩力和肾小球滤过，增加肾小管钠重吸收以及心脏和血管肥大。对AT2受体的功能了解较少。有证据表明，AT2受体抑制细胞增殖并逆转AT1诱导的肥大。实际上，这些受体被认为发挥相反的作用。
这类新引入的药物能够通过特异性阻断AT1受体亚型在受体水平抑制肾素-血管紧张素系统。这些药物诱导血管紧张素II作用的剂量依赖性阻断，导致血压降低、尿蛋白减少和肾小球硬化。据推测，AT1受体拮抗剂可能通过阻断血管紧张素II通过AT1受体的作用来提供终末器官保护，使AT2受体不受抑制。因此，这些药物可能降低心肌梗死以及由心脏、肾脏和血管结构改变引起的其他病症导致的发病率和死亡率。
