Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan.
J Pharmacol Sci. 2012;118(3):311-6. doi: 10.1254/jphs.11r11cp. Epub 2012 Feb 14.
Angiotensin II plays an important role in regulating blood pressure. Moreover, angiotensin II directly promotes organ damage by inducing expression of various genes, such as transforming growth factor (TGF)-β and matrix metalloproteinase (MMP)-9 precursors. Blockade of angiotensin II has been shown to not only lower blood pressure, but also to prevent cardiovascular and renal dysfunction and fibrosis. Inhibition of TGF-β and MMP-9 has also been shown to prevent cardiovascular and renal damage. A mast cell-produced enzyme, chymase, generates angiotensin II and also converts precursors of TGF-β and MMP-9 to their active forms. Chymase also strongly promotes accumulation of inflammatory cells. These multiple functions of chymase may play an important role in the development and promotion of various diseases. In fact, chymase inhibitors have been shown to prevent nonalcoholic steatohepatitis, intestinal inflammation, and adhesion formation after surgery and cardiovascular and renal damage. On the other hand, chymase inhibitors, unlike angiotensin-converting enzyme inhibitors and angiotensin II blockers, have no blood pressure-lowering effect despite blocking angiotensin II formation. Thus, chymase inhibitors may be useful for preventing damage to various organs via multiple mechanisms without lowering blood pressure.
血管紧张素 II 在调节血压方面发挥着重要作用。此外，血管紧张素 II 通过诱导转化生长因子 (TGF)-β和基质金属蛋白酶 (MMP)-9 前体等各种基因的表达，直接促进器官损伤。阻断血管紧张素 II 不仅可以降低血压，还可以预防心血管和肾脏功能障碍和纤维化。抑制 TGF-β和 MMP-9 也已被证明可以预防心血管和肾脏损伤。肥大细胞产生的一种酶糜酶可产生血管紧张素 II，还可将 TGF-β和 MMP-9 的前体转化为其活性形式。糜酶还强烈促进炎症细胞的积累。糜酶的这些多种功能可能在各种疾病的发展和促进中发挥重要作用。事实上，已经证明糜酶抑制剂可预防非酒精性脂肪性肝炎、肠道炎症以及手术后的粘连形成和心血管及肾脏损伤。另一方面，尽管抑制了血管紧张素 II 的形成，糜酶抑制剂与血管紧张素转换酶抑制剂和血管紧张素 II 受体阻滞剂不同，没有降低血压的作用。因此，糜酶抑制剂可能通过多种机制预防各种器官损伤而不降低血压。
