Angiotensin II: hemodynamic regulator or growth factor?
Angiotensin II: hemodynamic regulator or growth factor?
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血管紧张素II：血流动力学调节剂还是生长因子？
DOI：
10.1016/0022-2828(90)90086-h
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发表时间：
1990
影响因子：
5
通讯作者：
Katz,AM
中科院分区：
文献类型：
--
作者：
Katz,AM
我们对血管紧张素II作用的理解的演变可以用3种范式来描述，这些范式也表征了我们对心血管调节知识的发展[1]。第一个范例，器官生理学，描述了心脏在心肌收缩功能的长度依赖性变化方面的可变性能（Starling定律），以及Ang II作为升高血压的升压因子。随着向第二范式的转变，细胞生物化学和生物物理学，心脏性能的调节被解释为改变钙流量和改变心肌收缩力，而血管紧张素II的临床作用被理解为控制平滑肌收缩的钙流量的变化。第三种范式，基因表达（分子生物学），可能描述了这些调控机制中最具连续性和复杂性的。响应于各种化学和物理力的基因表达改变可以解释心脏性能长期调节的几个方面，即异质心肌细胞群体的结构和组成的适应性变化[1，35]。这第三个范例也描述了血管紧张素II的重要作用，增加蛋白质合成和促进细胞生长，似乎能够改善和加剧人类疾病，因此，这可能是不恰当的，主要是血管紧张素II作为一种血管收缩剂与继发性影响，诱导细胞肥大。相反，血管紧张素II可能来自原始生长因子，因为它利用Ca 2+介导其对基因表达的影响，后来在进化中获得了增加平滑肌张力和心肌收缩力的能力。这种观点认为，血管紧张素II可能是来自一种生长因子，提供了一个更清楚的了解CEI在心血管疾病患者中的作用，因为这些药物的作用可能是由于改变平滑肌和心肌细胞肥大的血压和平滑肌张力的变化。
The evolution of our understanding of the actions of Ang II can be described in terms of 3 paradigms that also characterize the development of our knowledge of cardiovascular regulation [1]. The first paradigm,organ physiology, described the variable performance of the heart in terms of length-dependent changes in myocardial contractile function (Starling's Law), and Ang II as a pressor factor that elevated blood pressure. With the shift to the second paradigm,cell biochemistry and biophysics, regulation of cardiac performance came to be explained by altered calcium fluxes and changing myocardial contractility, while the clinical effects of Ang II were understood in terms of changes in the calcium fluxes that control smooth muscle contraction. The third paradigm,gene expression(molecular biology), probably describes the most primitive—and complex—of these regulatory mechanisms. Altered gene expression in response to a variety of chemical and physical forces can explain several aspects of the long-term regulation of cardiac performance in terms of adaptative changes in the architecture and composition of a heterogeneous population of myocardial cells [1, 35]. This third paradigm also describes important effects of Ang II to increase protein synthesis and promote cell growth that appear able both to ameliorate and exacerbate human disease.It is, therefore, probably inappropriate to view Ang II mainly as a vasoconstrictor with secondary effects to induce cell hypertrophy. Instead, Ang II may have been derived from a primitive growth factor that, because it utilized Ca2+to mediate its effects on gene expression, later in evolution acquired the ability to increase smooth muscle tone and myocardial contractility. This view, that Ang II may have been derived from a growth factor, provides a clearer understanding of the effects of the CEI in patients with cardiovascular disease, as the effects of these drugs may be due as much to altered smooth muscle and myocardial cell hypertrophy as to changes in blood pressure and smooth muscle tone.