Williams B
Cardiovascular Research Institute, Leicester University Medical School, Leicester, UK.
Am J Cardiol. 2001 Apr 19;87(8A):10C-17C. doi: 10.1016/s0002-9149(01)01507-7.
Hypertension is associated with a number of adverse morphologic and functional changes in the cardiovascular system. These include remodeling of the left ventricle, alterations in the morphology and mechanical properties of the vasculature, and the development of endothelial dysfunction. Recent studies have shown that angiotensin II is capable of mediating these changes via its interaction with the angiotensin II type 1 receptor. These nonhemodynamic effects of angiotensin II are independent of its effect on blood pressure. Thus, elevated levels of angiotensin II may lead directly to many hypertension-associated pathologies. Recent evidence that mechanical strain, oxidized low-density lipoprotein cholesterol, and aldosterone can cause upregulation of angiotensin II type 1 receptors indicates that activation of the renin-angiotensin system is not necessary for the actions of angiotensin II to be amplified. Because the strain on the vessel wall may be increased under conditions of hypertension, increased arterial pressure may amplify the actions of angiotensin II without a discernible increase in plasma angiotensin II levels. In both the myocardium and the peripheral vasculature, fibrosis is a major component of the remodeling that occurs in hypertension. There is substantial evidence that transforming growth factor beta-1 (TGF-beta(1)) mediates angiotensin-II-induced fibrosis in patients with hypertension and in those with a variety of nephropathies. Mechanical strain also induces fibrosis in a mechanism mediated by TGF-beta(1). This cytokine thus represents a common pathway by which angiotensin II and increased arterial pressure may induce cardiovascular fibrosis.
高血压与心血管系统的一些不良形态学和功能变化相关。这些变化包括左心室重塑、血管形态和力学特性改变以及内皮功能障碍的发生。最近的研究表明，血管紧张素II能够通过与1型血管紧张素II受体相互作用介导这些变化。血管紧张素II的这些非血流动力学效应独立于其对血压的影响。因此，血管紧张素II水平升高可能直接导致许多与高血压相关的病理状况。最近有证据表明，机械牵张、氧化型低密度脂蛋白胆固醇和醛固酮可导致1型血管紧张素II受体上调，这表明肾素-血管紧张素系统的激活对于血管紧张素II作用的放大并非必要。由于在高血压情况下血管壁上的牵张可能增加，动脉压升高可能会放大血管紧张素II的作用，而血浆血管紧张素II水平并无明显升高。在心肌和外周血管系统中，纤维化是高血压时发生的重塑的主要组成部分。有大量证据表明，转化生长因子β-1（TGF-β(1)）介导高血压患者和各种肾病患者中血管紧张素II诱导的纤维化。机械牵张也通过TGF-β(1)介导的机制诱导纤维化。因此，这种细胞因子代表了血管紧张素II和动脉压升高可能诱导心血管纤维化的共同途径。
