Inward remodeling of resistance arteries requires reactive oxygen species-dependent activation of matrix metalloproteinases
Inward remodeling of resistance arteries requires reactive oxygen species-dependent activation of matrix metalloproteinases
复制标题
DOI：
10.1152/ajpheart.01066.2010
复制
发表时间：
2011-06-01
影响因子：
4.8
通讯作者：
Boone, Matthew
中科院分区：
文献类型：
--
作者：
Martinez-Lemus, Luis A.;Zhao, Guiling;Boone, Matthew
Martinez-Lemus LA, Zhao G, Galinanes EL, Boone M. Inward remodeling of resistance arteries requires reactive oxygen species-dependent activation of matrix metalloproteinases. Am J Physiol Heart Circ Physiol 300: H2005-H2015, 2011. First published April 1, 2011; doi: 10.1152/ajpheart.01066.2010.-Inward eutrophic remodeling is the most prevalent structural change of resistance arteries in hypertension. Sympathetic and angiotensin (ANG)-induced vasoconstriction has been associated with hypertension and with the production of matrix metalloproteinases (MMPs) and ROS. Therefore, we hypothesize that prolonged exposure to norepinephrine (NE) and ANG II induces arteriolar inward remodeling dependent on the activation of MMPs and the production of ROS. This hypothesis was tested on rat cremaster arterioles that were isolated, cannulated, pressurized, and exposed to either NE (10 (5.5) mol/l) + ANG II (10 (7) mol/l) or vehicle (control) for 4 h. The prolonged exposure to NE + ANG II induced inward remodeling, as evidenced by the reduced maximal arteriolar passive diameter observed after versus before exposure to the vasoconstrictor agonists. NE + ANG II also increased the arteriolar expression and activity of MMP-2 and the production of ROS as determined, respectively, by real-time RT-PCR, gel and in situ zymography, and the use of ROS-sensitive dyes with multiphoton microscopy. Inhibition of MMP activation (with GM-6001) or ROS production (with apocynin or tempol) prevented the NE + ANG II-induced inward remodeling. Inhibition of ROS production prevented the activation of MMPs and the remodeling process, whereas inhibition of MMP activation did not affect ROS production. These results indicate that prolonged stimulation of resistance arterioles with NE + ANG II induces a ROS-dependent activation of MMPs necessary for the development of arteriolar inward remodeling. These mechanisms may contribute to the structural narrowing of resistance vessels in hypertension.
