ACTIVATION OF ANGIOTENSINOGEN GENE IN CARDIAC MYOCYTES BY ANGIOTENSIN-II AND MECHANICAL STRETCH

Circulating and cardiac renin-angiotensin systems (RAS) play important roles in the development of cardiac hypertrophy. Mechanical stretch o f cardiac myocytes induces secretion of ANG II and evokes hypertrophic responses. Angiotensinogen is a unique substrate of the RAS. This stu dy was performed to examine the regulation of the angiotensinogen gene in cardiac myocytes in response to ANG II and stretch. ANG II and str etch significantly increased the levels of angiotensinogen mRNA in car diac myocytes. Actinomycin D completely inhibited ANG II- and stretch- mediated increases in angiotensinogen mRNA. Although CV-11974 abolishe d ANG II-mediated increases in mRNA level and promoter activity of the angiotensinogen gene, the inhibition of stretch-mediated activation b y CV-11974 was significant but not complete. These results indicate th at ANG II activates transcription of the angiotensinogen gene exclusiv ely via ANG II type 1-receptor pathway and that stretch activates such transcription mainly via the same pathway in cardiac myocytes. Furthe rmore, factors other than ANG II may also be involved in stretch-media ted activation of the angiotensinogen gene in cardiac myocytes.