Cardiac hypertrophy in Aryl hydrocarbon receptor null mice is correlated with elevated angiotensin II, endothelin-1, and mean arterial blood pressure

摘要: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates toxicity of xenobiotics, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. Genetic deletion the AhR leads to cardiac hypertrophy, suggesting role for in cardiovascular physiology and disease; however, pathways involved development hypertrophy have not been determined. Thus, we investigated (1) pressure overload using indwelling catheters (2) vasoactive peptides endothelin-1 (ET-1) angiotensin II (Ang II), assessed by RIA, progression AhR-null mice. Histochemical analysis, expression marker genes, echocardiography were used assess degree hypertrophy. mice developed elevated mean arterial pressures (MAP) 5 months, which was associated with two- ninefold increase plasma ET-1 Ang II, respectively, compared wild-type. Captopril-treatment (4 mg/kg) from 2 months age significantly decreased MAP but did affect ET-1. Further, captopril improved function reduced evidenced reduction left ventricle mass, internal dimension, molecular markers. Captopril also fibrosis heart kidney. These findings show hypertrophic growth mediated, part, II.