Katoh M, Egashira K, Mitsui T, Takeshita A, Narita H
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.
J Cardiovasc Pharmacol. 2000 Jun;35(6):932-6. doi: 10.1097/00005344-200006000-00016.
We investigated effects of the angiotensin-converting enzyme (ACE) inhibitor imidapril and the angiotensin II type 1 (AT1) antagonist candesartan cilexetil on cardiac plasminogen activator inhibitor-1 (PAI-1) expression in rats. Cardiac PAI-1 mRNA levels were increased after a 7-day treatment with the nitric oxide (NO) synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). PAI-1 immunoreactivity was increased in the coronary arteries. Treatment with imidapril significantly prevented the L-NAME-induced increase in the gene expression and immunoreactivity of PAI-1, but candesartan cilexetil showed no such effect. This study provides the first evidence of differential effects of ACE inhibition and AT1 antagonism on cardiac PAI-1 expression in vivo.
我们研究了血管紧张素转换酶(ACE)抑制剂咪达普利和血管紧张素II 1型(AT1)拮抗剂坎地沙坦酯对大鼠心脏纤溶酶原激活物抑制剂-1(PAI-1)表达的影响。在用一氧化氮(NO)合成抑制剂N(ω)-硝基-L-精氨酸甲酯(L-NAME)进行7天治疗后,心脏PAI-1 mRNA水平升高。冠状动脉中PAI-1免疫反应性增强。咪达普利治疗可显著阻止L-NAME诱导的PAI-1基因表达和免疫反应性增加,但坎地沙坦酯未显示出此类作用。本研究首次提供了ACE抑制和AT1拮抗对体内心脏PAI-1表达具有不同作用的证据。