Lüscher T F
Department of Medicine, University Hospital Basel, Switzerland.
Basic Res Cardiol. 1993;88 Suppl 1:15-24. doi: 10.1007/978-3-642-72497-8_2.
The renin angiotensin system and endothelium-derived vasoactive substances are both important regulators of vascular tone. Recent evidence suggests that the two systems may be tightly interconnected and drugs interfering with one system may also affect the other. Beside the circulating renin angiotensin system, a vascular wall renin angiotensin system has been postulated and various components of it have been demonstrated in endothelial and vascular smooth muscle cells. Of particular importance is the angiotensin converting enzyme (ACE) which is identical to kininase II, which breaks down bradykinin into inactive components. Bradykinin is a potent activator of the L-arginine nitric oxide system (endothelium-derived relaxing factor). Hence, ACE-inhibitors not only deactivate the pressor system, but increase the local concentrations of bradykinin and thereby stimulate a potent endothelium-derived vasodilator system. Angiotensin II not only can activate vascular smooth muscle cells (where it causes contraction and proliferation), but also endothelial cells. In certain blood vessels, angiotensin II can stimulate prostacyclin production; in addition, angiotensin II activates endothelin messenger RNA in endothelial cells. This activation of the endothelin vasopressor system increases vascular tone and enhances the local vasoconstrictor responses (due to the amplifying effects of endothelin on noradrenaline- and serotonin-induced contractions). Although the acute effects of ACE-inhibitors in isolated blood vessels are restricted to inhibition of angiotensin I-induced contractions and augmentation of bradykinin-induced endothelium-dependent relaxations, chronic therapy with the drugs appears to enhance endothelium-dependent responses to several agonists, particularly in hypertensive animals. Hence, this mechanism of action of ACE-inhibitors may account for an important vascular protective effect of the drugs. Thus, in summary, the renin angiotensin system and endothelium-derived vasoactive substances are tightly interconnected. This may be important under physiological and pathophysiological conditions, and is of importance for the action of currently available cardiovascular drugs, in particular, ACE-inhibitors.
肾素血管紧张素系统和内皮源性血管活性物质都是血管张力的重要调节因子。最近的证据表明，这两个系统可能紧密相连，干扰一个系统的药物可能也会影响另一个系统。除了循环肾素血管紧张素系统外，已推测存在血管壁肾素血管紧张素系统，并且在内皮细胞和血管平滑肌细胞中已证实了其各种成分。特别重要的是血管紧张素转换酶（ACE），它与激肽酶II相同，可将缓激肽分解为无活性成分。缓激肽是L-精氨酸一氧化氮系统（内皮源性舒张因子）的强效激活剂。因此，ACE抑制剂不仅使升压系统失活，还增加了缓激肽的局部浓度，从而刺激了强效的内皮源性血管舒张系统。血管紧张素II不仅可以激活血管平滑肌细胞（使其收缩和增殖），还可以激活内皮细胞。在某些血管中，血管紧张素II可以刺激前列环素的产生；此外，血管紧张素II可激活内皮细胞中的内皮素信使RNA。内皮素升压系统的这种激活会增加血管张力，并增强局部血管收缩反应（由于内皮素对去甲肾上腺素和5-羟色胺诱导的收缩的放大作用）。尽管ACE抑制剂在离体血管中的急性作用仅限于抑制血管紧张素I诱导的收缩和增强缓激肽诱导的内皮依赖性舒张，但长期使用这些药物似乎会增强对几种激动剂的内皮依赖性反应，尤其是在高血压动物中。因此，ACE抑制剂的这种作用机制可能解释了该药物重要 的血管保护作用。因此，总之，肾素血管紧张素系统和内皮源性血管活性物质紧密相连。这在生理和病理生理条件下可能很重要，并且对于目前可用的心血管药物，特别是ACE抑制剂的作用也很重要。
