Kim S, Ohta K, Hamaguchi A, Omura T, Tominaga K, Yukimura T, Miura K, Tanaka M, Iwao H
Department of Pharmacology, Osaka City University Medical School, Japan.
Br J Pharmacol. 1994 Nov;113(3):662-3. doi: 10.1111/j.1476-5381.1994.tb17042.x.
Fibronectin plays an important role in various vascular diseases. A subpressor (200 ng kg-1 min-1) or pressor (1000 ng kg-1 min-1) dose of angiotensin II was continuously infused into rats by osmotic minipump for various times, to investigate the effects on aortic fibronectin gene expression. In rats infused with a subpressor dose of angiotensin II in which blood pressure was normal for 3 days, aortic fibronectin mRNA levels started to increase by 1.4 fold at 12 h and reached the maximal levels (increased by 3.1 fold) at 3 days. Treatment with TCV-116 (3 mg kg-1 day-1), a non-peptide selective AT1 receptor antagonist, completely inhibited the angiotensin II-induced increase in aortic fibronectin mRNA, while hydralazine (10 mg kg-1 day-1) did not block this effect. Similar results were also obtained for a pressor dose of angiotensin II. Thus, angiotensin II directly stimulates aortic fibronectin gene expression in vivo, which is mediated by the AT1 receptor but not by blood pressure.
纤连蛋白在多种血管疾病中起重要作用。通过渗透微型泵将亚降压剂量（200 ng·kg⁻¹·min⁻¹）或升压剂量（1000 ng·kg⁻¹·min⁻¹）的血管紧张素II连续输注到大鼠体内不同时间，以研究其对主动脉纤连蛋白基因表达的影响。在输注亚降压剂量血管紧张素II且血压正常3天的大鼠中，主动脉纤连蛋白mRNA水平在12小时时开始增加1.4倍，并在3天时达到最高水平（增加3.1倍）。用非肽选择性AT1受体拮抗剂TCV - 116（3 mg·kg⁻¹·天⁻¹）治疗可完全抑制血管紧张素II诱导的主动脉纤连蛋白mRNA增加，而肼屈嗪（10 mg·kg⁻¹·天⁻¹）则不能阻断这种作用。对于升压剂量的血管紧张素II也获得了类似结果。因此，血管紧张素II在体内直接刺激主动脉纤连蛋白基因表达，这是由AT1受体介导的，而非血压介导。
