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传统观念认为,肾素-血管紧张素系统(RAS)为一内分泌系统。最近研究表明,在许多组织局部存在肾素和血管紧张素原基因及其产物。许多组织能合成血管紧张素这一概念改变了人们对 RAS 生理的认识。在循环的 RAS 以外,这些潜在的自靶促分泌-旁靶促分泌系统(autocrine-paracrine system)可能对调节局部组织功能也起到很重要的作用。它们的活性会影响 RAS 抑制剂的药理效应。例如,资料表明组织血管紧张素转换酶(ACE)是 ACE 抑制剂的主要作用部位,因此 ACE 抑制剂的作用时间主要取决于组织 ACE 被抑制的时间,而不是药物的血清半衰期,各种ACE 抑制剂的区别在于其对组织 RAS 的不同效应。
The traditional wisdom is that the renin-angiotensin system (RAS) is an endocrine system. Recent studies have shown that there are localized renin and angiotensinogen genes and their products in many tissues. The concept that many organizations are able to synthesize angiotensin alters one’s perception of RAS physiology. In addition to circulating RAS, these potential autocrine-paracrine systems may also play important roles in regulating local tissue function. Their activity affects the pharmacological effects of RAS inhibitors. For example, data suggest that tissue angiotensin-converting enzyme (ACE) is a major site of action of ACE inhibitors and thus the duration of action of an ACE inhibitor depends primarily on the time of tissue ACE inhibition and not on the serum half-life of the drug. Various ACE inhibitory The difference between agents is their different effect on tissue RAS.