AIM: Atherosclerosis is a cardiovascular disease; however, there is little information on signal transduction for vascular function in the early stage of atherosclerosis. In this work, we investigated the role of Rho/Rho-kinase and nitrogen oxide (NO)/cyclic GMP (cGMP) signaling pathways in the aorta prior to atherosclerosis. METHODS: Tension, the expression of RhoA protein, Rho-kinase activity and the cGMP level were measured using endothelium-intact or -denuded aorta prepared from apolipoprotein E-deficient (apoE-KO) and C57BL/6 wild-type (WT) mice at 2 months of age. RESULTS: Phenylephrine (PE) induced less maximal contraction in the endothelium-denuded aorta from apoE-KO than from WT mice. A Rho-kinase inhibitor (Y-27632) reduced more effectively the contraction of apoE-KO than WT mice, but their RhoA proteins and Rho-kinase activities were not so different. Acetylcholine caused larger relaxation of the PE-stimulated, endothelium-intact aorta in apoE-KO due to endothelial NO release than WT mice. The basal cGMP level in the endothelium-intact aorta of apoE-KO mice was higher than that of WT. CONCLUSIONS: Smooth muscle contraction via alpha(1)-adrenergic receptor shows higher dependency on Rho-kinase activity, suggesting down-regulation of the mechanism different from Rho/Rho kinase signaling in the aorta prior to atherosclerosis. Endothelium-dependent relaxation is also intensified through the NO/cGMP pathway.
AIM: Atherosclerosis is a cardiovascular disease; however, there is little information on signal transduction for vascular function in the early stage of atherosclerosis. In this work, we investigated the role of Rho/Rho-kinase and nitrogen oxide (NO)/cyclic GMP (cGMP) signaling pathways in the aorta prior to atherosclerosis. METHODS: Tension, the expression of RhoA protein, Rho-kinase activity and the cGMP level were measured using endothelium-intact or -denuded aorta prepared from apolipoprotein E-deficient (apoE-KO) and C57BL/6 wild-type (WT) mice at 2 months of age. RESULTS:Phenylephrine (PE) induced less maximal contraction in the endothelium-denuded aorta from apoE-KO than from WT mice. A Rho-kinase inhibitor (Y-27632) reduced more effectively the contraction of apoE-KO than WT mice, but their RhoA proteins and Rho-kinase activities were not so different. Acetylcholine caused larger relaxation of the PE-stimulated, endothelium-intact aorta in apoE-KO due to endothelial NO release than WT mice. The basal cGMP level in the endothelium-intact aorta of apoE-KO mice was higher than that of WT. CONCLUSIONS: Smooth muscle contraction via alpha(1)-adrenergic receptor shows higher dependency on Rho-kinase activity, suggesting down-regulation of the mechanism different from Rho/Rho kinase signaling in the aorta prior to atherosclerosis. Endothelium-dependent relaxation is also intensified through the NO/cGMP pathway.
Authors: Gregory E Bigford; Valerie C Bracchi-Ricard; Robert W Keane; Mark S Nash; John R Bethea Journal: ASN Neuro Date: 2013-09-04 Impact factor: 4.146