Vasoconstriction‐induced inward remodeling of isolated arterioles involves reactive oxygen species‐dependent activation of matrix metalloproteinases

Abstract

We previously demonstrated that inward remodeling induced by prolonged agonist‐induced vasoconstriction in isolated arterioles requires reactive oxygen species (ROS) generation and activation of matrix metalloproteinases (MMPs). We hypothesize that ROS participate in the vasoconstriction‐induce inward remodeling process in part by promoting MMP activation. This hypothesis was tested in isolated and pressurized (60 mmHg) rat cremaster arterioles exposed to norepinephrine (NE, 10−5.5 M) plus angiotensin‐II (Ang‐II, 10−7 M) for 4 hours. Prolonged vasoconstriction induced inward remodeling and increased the gelatinolytic activity of arterioles (P<0.05). ROS‐inhibition with apocynin, tempol, or the Rac‐inhibitor, NSC, significantly affected the development of inward remodeling and reduced the arteriolar gelatinolytic activity induced by NE and Ang‐II. These results indicate that during prolonged vasoconstriction MMPs are in part activated through a pathway dependent on the generation of ROS, and that ROS are required for the acute remodeling of the vascular wall. As MMP‐inhibition prevents the development of inward remodeling, these results suggest that vasoconstriction‐induced inward remodeling in resistance vessels is associated with ROS‐dependent activation of MMPs.Funded by AHA and NIH.