Plasminogen activator inhibitor-1 deficiency prevents hypertension and vascular fibrosis in response to long-term nitric oxide synthase inhibition
Plasminogen activator inhibitor-1 deficiency prevents hypertension and vascular fibrosis in response to long-term nitric oxide synthase inhibition
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DOI：
10.1161/hc3301.092803
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发表时间：
2001-08-14
期刊：
影响因子：
37.8
通讯作者：
Vaughan, DE
中科院分区：
文献类型：
--
作者：
Kaikita, K;Fogo, AB;Vaughan, DE
背景-一氧化氮合酶(NOS)的长期抑制被认为会导致高血压和血管周围纤维化。最近的证据也表明，长期的NOS抑制诱导了血管组织中纤溶酶原激活物抑制物-1(PAM)的表达，PAI-1可能参与了化学或电离损伤后纤维化的发展。在这些观察的基础上，我们假设PAI-1可能影响血管对N-omega-硝基-L-精氨酸甲酯(L-NAME)长期抑制一氧化氮合酶的反应。方法和结果-我们比较了PAI-1基因缺陷(PAI-1(-/-))和野生型(WT)雄性小鼠(每组6只)收缩压和冠状动脉血管周围纤维化的时间变化。在基线时，两组之间的血压没有显著差异。L治疗2周后，两组患者的血压均升高。在为期8周的研究期间，WT动物的收缩压上升到141+/-3 nUN汞，而PAL-1(-/-)小鼠的收缩压上升到112+/-4分钟汞(P
Background-Long-term inhibition of nitric oxide synthase (NOS) is known to induce hypertension and perivascular fibrosis. Recent evidence also suggests that long-term NOS inhibition induces expression of plasminogen activator inhibitor-1 (PAM) in vascular tissues and that PAI-1 may contribute to the development of fibrosis after chemical or ionizing injury. On the basis of these observations, we hypothesized that PAI-1 may influence the vascular response to long-term NOS inhibition by N-omega -nitro-L-arginine methyl ester (L-NAME).Methods and Results-We compared the temporal changes in systolic blood pressure and coronary perivascular fibrosis in PAI-1-deficient (PAI-1(-/-)) and wild-type (WT) male mice (N=6 per group). At baseline, there, were no significant differences in blood pressure between groups. After initiation of L-NAME, systolic blood pressure increased in both groups at 2 weeks. Over an 8-week study period, systolic blood pressure increased to 141 +/-3 nun Hg in WT animals versus 112 +/-4 min Hg in PAL-1(-/-) mice (P