ANGIOTENSINOGEN GENE-EXPRESSION IS INDUCED BY CYCLICAL MECHANICAL STRETCH IN CULTURED RAT CARDIOMYOCYTES

The effect of cyclical mechanical stretch on angiotensinogen gene expression was examined using a neonatal rat cardiocyte culture system. Cultured cardiocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation, at 60 cycles/min. The angiotensinogen gene was activated 2 to 5 fold after stretch for 3 to 24 hr, as shown by quantitative reverse transcription polymerase chain reaction. The 5'-flanking region of the angiotensinogen promoter was activated after stretch for 24 hr. This gene expression could be completely suppressed by losartan, a specific antagonist of angiotensin II receptor. These results indicate that (1) cyclical mechanical stretching of cardiocytes is a good model for the study of cardiac hypertrophy-related gene expression; (2) cyclical stretch up-regulates expression of the angiotensinogen gene and (3) the increase in promoter activity may contribute to the induction of angiotensinogen mRNA by cyclical stretch. (C) 1995 Academic Press, Inc.