Reactive oxygen species-induced vascular contraction and Ca2+ sensitization in rat aorta are mediated through activation of the Rho/Rho kinase signaling pathway, but not Ca2+-independent PKC.
Evidence indicates that both the Rho/Rho kinase signaling pathway and reactive oxygen species (ROS) such as superoxide and H(2)O(2) are involved in the pathogenesis of hypertension. This study aimed to determine whether ROS-induced vascular contraction is mediated through activation of Rho/Rho kinase. Rat aortic rings (endothelium denuded) were isolated and placed in organ chambers for measurement of isometric force development. ROS were generated by a xanthine (X)-xanthine oxidase (XO) mixture. The antioxidants tempol (3 mM) and catalase (1,200 U/ml) or the XO inhibitor allopurinol (400 microM) significantly reduced X/XO-induced contraction. A Rho kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl-N-4-pyridil)cyclohexanecarboxamide dihydrochloride (Y-27632), decreased the contraction in a concentration-dependent manner; however, the Ca(2+)-independent protein kinase C inhibitor rottlerin did not have an effect on X/XO-induced contraction. Phosphorylation of the myosin light chain phosphatase target subunit (MYPT1) was increased by ROS, and preincubation with Y-27632 blocked this increased phosphorylation. Western blotting for cytosolic and membrane-bound fractions of Rho showed that Rho was increased in the membrane fraction by ROS, suggesting activation of Rho. These observations demonstrate that ROS-induced Ca(2+) sensitization is through activation of Rho and a subsequent increase in Rho kinase activity but not Ca(2+)-independent PKC.
Jin et al. (Wed,) conducted a other in Vascular contraction / Hypertension pathogenesis. Reactive oxygen species (ROS) generated by xanthine-xanthine oxidase vs. Inhibitors (tempol, catalase, allopurinol, Y-27632, rottlerin) was evaluated on Isometric force development (vascular contraction) and MYPT1 phosphorylation. Reactive oxygen species-induced vascular contraction and Ca2+ sensitization in rat aorta are mediated through activation of the Rho/Rho kinase signaling pathway, but not Ca2+-independent PKC.