Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Trends Cardiovasc Med. 1997 Nov;7(8):307-11. doi: 10.1016/S1050-1738(97)00089-3.
Kallistatin, first discovered as a human kallikrein-binding protein in the circulation, shares high homology with other plasma serine proteinase inhibitors (serpins). It forms a covalently linked complex with tissue kallikrein and inhibits kallikrein's activity. Substantial evidence has accumulated in recent years indicating that kallistatin may play a role in blood pressure regulation independent of its interaction with tissue kallikrein. Intravenous injection of kallistatin into rats and mice results in a rapid and transient reduction of blood pressure in a dose-dependent manner. Functional analysis in transgenic mice over-expressing rat kallikrein-binding protein, an analogue of human kallistatin, revealed that these mice have significantly lower blood pressure compared with control littermates. Adenovirus-mediated delivery of the human kallistatin gene can cause significant blood pressure reductions for 4 weeks in spontaneously hypertensive rats. Finally, kallistatin can induce vasorelaxation in isolated rat aortic rings and reduce renal perfusion pressure in the isolated, perfused kidney. Together, these findings suggest a direct role for kallistatin in regulating blood pressure and raise the possibility for the development of new pharmacological treatments for hypertension. (Trends Cardiovasc Med 1997;7:307-311). © 1997, Elsevier Science Inc.
激肽素最初作为一种人激肽释放酶结合蛋白在循环中被发现，与其他血浆丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂）具有高度同源性。它与组织激肽形成共价连接的复合物并抑制激肽的活性。近年来，大量证据表明，激肽素可能在不与其与组织激肽相互作用的情况下，在血压调节中发挥作用。将激肽素静脉注射到大鼠和小鼠中，会导致血压迅速而短暂地呈剂量依赖性下降。在过表达大鼠激肽释放酶结合蛋白（人激肽素类似物）的转基因小鼠中的功能分析表明，与对照同窝仔相比，这些小鼠的血压明显降低。腺病毒介导的人激肽素基因的传递可导致自发性高血压大鼠的血压显著降低长达 4 周。最后，激肽素可引起分离的大鼠主动脉环的血管舒张，并降低分离灌注肾脏的肾灌注压。总之，这些发现表明激肽素在调节血压方面具有直接作用，并为高血压的新药物治疗方法的发展提供了可能性。（趋势心血管医学 1997; 7:307-311）。© 1997 年，Elsevier Science Inc.
