Changes in endogenous sulfur dioxide pathway in angiotensin II- induced myocardial hypertrophy in mice

Abstract

Objective To explore the changes in the endogenous sulfur dioxide (SO2) pathway in the myocardial hypertrophy induced by the angiotensin Ⅱ(Ang Ⅱ) in mice. Methods Fourteen healthy C57BL mice, 9 weeks old, were randomly divided into control group(n=7) and Ang Ⅱ group(n=7), and capsule osmotic pump with pre-loaded 9 g/L saline and Ang Ⅱ was implanted into the back of each mouse subcutaneously.After 2 weeks, the mice were executed.The heart weight/body weight (HW/BW) and the left heart weight/full heart weight (LVW/HW) of the mice were measured.The microstructure of the cardiac myocyte was observed by hematoxylin-eosin (HE) staining under the microscope.The expression of myocardial alpha myosin heavy chain (α-MHC) was detected by immunohistochemistry and Western blot methods.SO2 enzymes aspartate aminotransferase 1 (AAT1) and AAT2 protein expression were detected by Western blot method.Myocardial SO2 content and AAT activity were measured by high performance liquid chromatography with fluorimetric detection and colometric method. Results Compared with control group, the HW/BW and LVW/HW in mice of Ang Ⅱ group were significantly increased(all P<0.01), the cardiac myocytes were hypertrophy, and α-MHC positive staining in the cytoplasm of myocardium was weakened.Moreover, Western blot data showed that α-MHC protein expression in heart tissue of Ang Ⅱ-treated mice was decreased significantly (all P<0.05). Simultaneously, the data showed that AAT2 protein expression, SO2 content and AAT activity in heart tissue of Ang Ⅱ-treated mice were also decreased markedly[(1.093±0.131) μmol/g protein vs.(0.737±0.233) μmol/g protein, P<0.05; (7.979±1.317) U/mg protein vs.(6.470±0.516) U/mg protein, P<0.01]. Furthermore, there was a negative correlation between LVW/HW and cardiac SO2 content in heart tissue (r=-0.56, P<0.05). Conclusions Myocardial endogenous SO2/AAT2 pathway is down-regulated in the development of myocardial hypertrophy induced by Ang Ⅱ in mice. Key words: Myocardial hypertrophy; Sulfur dioxide; Angiotensin Ⅱ