Rho kinase activation and gene expression related to vascular remodeling in normotensive rats with high angiotensin I-converting enzyme levelsReportar como inadecuado




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Resumen

The RhoA-Rho kinase ROCK pathway is a new mechanism of remodeling and vasoconstriction. Few data are available regarding ROCK activation when angiotensin I-converting enzyme is high and blood pressure is normal. We hypothesized that ROCK is activated in the vascular wall in normotensive rats with genetically high angiotensin I converting enzyme levels, and it causes increased vascular expression of genes promoting vascular remodeling and also oxidative stress. Aortic ROCK activation, mRNA and protein levels of monocyte chemoattractant protein-1, transforming growth factor TGF-beta1, and plasminogen activator inhibitor-1 PAI-1, NADPH oxidase activity, and O-2.- production were measured in normotensive rats with genetically high Brown Norway BN and low Lewis angiotensin-I-converting enzyme levels and in BN rats treated with the ROCK antagonist fasudil 100 mg-kg per day for 7 days. ROCK activation was 12-fold higher in BN versus Lewis rats P<0.05 and was reduced with fasudil by 100% P<0.05. Aortic TGF-beta 1, PAI-1, and monocyte chemoattractant protein-1 mRNA levels were higher in BN versus Lewis rats by 300%, 180%, and 1000%, respectively P<0.05. Aortic TGF-beta 1, PAI-1, and monocyte chemoattractant protein-1 protein levels were higher in BN versus Lewis rats P<0.05. Fasudil reduced TGF-beta 1 and PAI-1 mRNA and TGF-beta 1, PAI-1, and monocyte chemoattractant protein-1 protein aortic levels to those observed in Lewis rats. Aortic reduced nicotinamide-adenine dinucleotide phosphate oxidase activity and .O-2- production were increased by 88% and 300%, respectively, in BN rats P<0.05 and normalized by fasudil. In conclusion, ROCK is significantly activated in the aortic wall in normotensive rats with genetically high angiotensin-I-converting enzyme and angiotensin II, and it causes activation of genes that promote vascular remodeling and also increases vascular oxidative stress.



Autor: Rivera, Paulina; - Ocaranza, María Paz; - Lavandero González, Sergio; - Jalil Milad, Jorge; -

Fuente: http://repositorio.uchile.cl/



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