Role of NO in flow-induced remodeling of the rabbit common carotid artery

被引:302
作者
Tronc, F
Wassef, M
Esposito, B
Henrion, D
Glagov, S
Tedgui, A
机构
[1] HOP LARIBOISIERE, INSERM, U141, F-75475 PARIS, FRANCE
[2] HOP LARIBOISIERE, DEPT PATHOL, INST FED RECH CIRCULAT LARIBOISIERE, F-75475 PARIS, FRANCE
[3] UNIV CHICAGO, DEPT PATHOL, CHICAGO, IL 60637 USA
关键词
endothelium; wall shear stress; vascular enlargement; hyperplasia; smooth muscle cell;
D O I
10.1161/01.ATV.16.10.1256
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Flow-induced changes in Vessel caliber tend to restore baseline wall shear stress (WSS) and have been reported to be endothelium-dependent. To investigate the role of endothelium-derived nitric oxide (NO) in the adaptive increase in artery diameter in response to a chronic increase in blood flow, an arteriovenous fistula was constructed between the left common carotid artery (CCA) and the external jugular vein in 22 New Zealand White rabbits, and NO synthesis was inhibited in 14 animals by long-term administration of N-G-nitro-L-arginine-methyl ester (L-NAME) in drinking water given for 4 weeks. The remaining 8 animals served as controls. Mean arterial blood pressure was not significantly altered by L-NAME treatment (91+/-2 in control versus 98+/-3 mm Hg in L-NAME-treated rabbits). Blood flow significantly increased in the left CCA in both groups but was lower in L-NAME-treated than control animals (106.1+/-10.7 versus 196.2+/-32.3 mL/min, P<.003). The diameter of the flow-loaded left CCA also increased significantly in both groups compared with the right CCA (2.15+/-0.12 and 2.54+/-0.1 mm, respectively, P<.02), but the increase was less in the L-NAME-treated than the control group (3.24+/-0.09 and 4.64+/-0.17 mm, respectively, P<.0001). The diameter of the anastomosed veins was also increased but to a much lesser degree in L-NAME-treated animals than in controls (4.14+/-0.29 versus 7.94+/-0.51 mm, P<.0001). As a result of artery enlargement, WSS was normalized in the Bow-loaded left CCA of the control group (8.87+/-0.77 dynes/cm(2)) regardless of blood flow values. In L-NAME-treated animals, however, WSS was only partially regulated, the mean value being significantly increased (18.7+/-2.2 dynes/cm(2), P<.006). Moreover, a highly significant positive correlation between WSS and blood how was obtained in L-NAME-treated animals (r=.84, P<.0001). We also found remodeling of the artery wall, with a larger increase in the medial cross-sectional area associated with an increased number of smooth muscle cells, in the control group compared with the L-NAME-treated group (0.75+/-0.09 versus 0.49+/-0.04 mm(2) and 4504+/-722 versus 2717+/-282 cells/mm(2), P<.03). We conclude that NO plays a role in the increase of vessel caliber in response to chronic increase in blood flow. As yet unidentified additional metabolic processes appear to be necessary for a complete regulatory response.
引用
收藏
页码:1256 / 1262
页数:7
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