Cody R J
Drugs. 1984 Aug;28(2):144-69. doi: 10.2165/00003495-198428020-00004.
The renin-angiotensin system is an important regulator of vascular resistance in many patients with hypertension and congestive heart failure. To quantitatively evaluate this contribution requires correlation of markers of the renin-angiotensin system with haemodynamic parameters, notably blood pressure, cardiac output, and calculated systemic vascular resistance. In addition, to determine ventricular loading properties, assessment of cardiac filling pressures is also required. The availability of specific pharmacological inhibitors of the renin-angiotensin system greatly enhances such correlation, as the haemodynamic consequence of blocking the renin-angiotensin system can then more fully identify its contribution. In the last decade, highly specific pharmacological inhibitors have become available to serve such a purpose. Renin inhibitory peptides, and renin-specific antibodies can block the rate-limiting step of the renin-angiotensin cascade: namely, the cleavage of 4 amino acids from the angiotensinogen substrate by renin. However, this method of blockade is still at the early stages of investigation. More readily available are converting enzyme inhibitors which block the formation of angiotensin II, the potent vasoconstrictor which mediates increased systemic vascular resistance, and angiotensin II analogues which compete with endogenous angiotensin II for vascular and adrenal receptors. Although hypertension and chronic congestive heart failure are clinically distinct entities in many respects, their common bond is the fact that both pathological mechanisms are mediated by an increase of systemic vascular resistance. The implications of blocking the resulting vasoconstriction in both entities are therefore quite similar. This review summarises our present knowledge of the contribution of the renin-angiotensin system to the vasoconstriction of hypertension and congestive heart failure, and also summarises the haemodynamic consequences of such inhibition. The implications of the response to these specific pharmacological probes, as well as their limitations, are discussed. Their importance rests not only in their therapeutic application, but also in their contribution as probes for pathophysiological mechanisms of vasoconstriction in cardiovascular disease.
肾素-血管紧张素系统是许多高血压和充血性心力衰竭患者血管阻力的重要调节因子。要定量评估这一作用，需要将肾素-血管紧张素系统的标志物与血流动力学参数相关联，尤其是血压、心输出量和计算得出的全身血管阻力。此外，为了确定心室负荷特性，还需要评估心脏充盈压。肾素-血管紧张素系统特异性药理抑制剂的出现极大地增强了这种相关性，因为阻断肾素-血管紧张素系统的血流动力学后果能够更全面地确定其作用。在过去十年中，已经有了用于此目的的高特异性药理抑制剂。肾素抑制肽和肾素特异性抗体可阻断肾素-血管紧张素级联反应的限速步骤，即肾素从血管紧张素原底物上切割下4个氨基酸。然而，这种阻断方法仍处于研究初期。更易于获得的是转换酶抑制剂，它可阻断血管紧张素II的形成，血管紧张素II是介导全身血管阻力增加的强效血管收缩剂，还有血管紧张素II类似物，它可与内源性血管紧张素II竞争血管和肾上腺受体。尽管高血压和慢性充血性心力衰竭在许多方面是临床上不同的病症，但它们的共同联系在于这两种病理机制均由全身血管阻力增加介导。因此，在这两种病症中阻断由此产生的血管收缩的意义非常相似。本综述总结了我们目前关于肾素-血管紧张素系统对高血压和充血性心力衰竭血管收缩作用的认识，也总结了这种抑制的血流动力学后果。讨论了对这些特异性药理探针反应的意义及其局限性。它们的重要性不仅在于其治疗应用，还在于它们作为心血管疾病血管收缩病理生理机制探针的作用。
