α1-adrenoceptor stimulation directly induces growth of vascular wall in vivo
α1-adrenoceptor stimulation directly induces growth of vascular wall in vivo
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DOI：
10.1152/ajpheart.00218.2002
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发表时间：
2002-10-01
影响因子：
4.8
通讯作者：
Faber, JE
中科院分区：
文献类型：
--
作者：
Erami, C;Zhang, H;Faber, JE
先前的研究表明，去甲肾上腺素是直接营养血管壁已混淆伴随血流动力学紊乱。在此，在大鼠颈动脉附近植入一个连接渗透微型泵的微导管，在血管周围以低于改变动脉压阈值1,000倍的全身水平给药2周。去甲肾上腺素使管腔和外膜面积及周长分别减少10%、14%和5%（均P < 0.05）;非亚型特异性α 1肾上腺素受体（AR）拮抗剂无影响。当在球囊损伤时开始时，2周的去甲肾上腺素使管腔损失增加45%，使新生内膜面积增加64%，胶原含量增加33%，并使血管周长减少5%（均P < 0.05）。α（1）-AR拮抗剂使新生内膜面积减少33%（均P < 0.05）。α（1）A-AR拮抗剂使管腔丢失减少70%，新生内膜面积减少54%，周长减少84%，外膜增厚减少87%（均P < 0.05），而α（1B）-、α（1D）-、α（2）-和β-AR拮抗剂则无作用。这些是第一次在体内研究表明，去甲肾上腺素是直接营养血管壁和增强损伤诱导的内膜病变生长。
Previous studies suggesting that norepinephrine is directly trophic for the vascular wall have been confounded by concomitant hemodynamic disturbances. Herein, a microcatheter connected to an osmotic minipump was implanted adjacent to the rat carotid for 2-wk perivascular suffusion of agents at systemic levels similar to1,000 times below the threshold for altering arterial pressure. Norepinephrine decreased lumen and adventitial areas and circumference by 10, 14, and 5%, respectively (all P < 0.05); a nonsubtype-specific α(1)-adrenoceptor (AR) antagonist had no effect. When begun at the time of balloon injury, 2-wk norepinephrine increased lumen loss by 45%, increased neointimal area by 64% and collagen content by 33%, and reduced vessel circumference by 5% (all P < 0.05). alpha(1)-AR antagonists decreased neointimal area by 33% (all P < 0.05). α(1)A-AR antagonist reduced lumen loss by 70%, neointimal area by 54%, circumference decline by 84%, and adventitial thickening by 87% (all P < 0.05), whereas alpha(1B)-, alpha(1D)-, alpha(2)- and beta-AR antagonists were without effect. These are the first in vivo studies demonstrating that norepinephrine is directly trophic for the vascular wall and augments injury-induced intimal lesion growth.