ANGIOTENSIN RECEPTOR REGULATES CARDIAC-HYPERTROPHY AND TRANSFORMING GROWTH FACTOR-BETA(1) EXPRESSION

The role of angiotensin II via the angiotensin type 1 or type 2 recept or in the development of cardiac hypertrophy was determined in adult m ale Sprague-Dawley rats subjected to coarctation of the abdominal aort a. Five groups of animals were studied: coarctation, coarctation plus DuP 753, coarctation plus PD 123319, sham plus DuP 753, or sham operat ion. Type 1 receptor blockade was accomplished with DuP 753 given in t he drinking water and type 2 blockade with PD 123319 delivered by osmo tic minipumps beginning with the day of surgery until 72 hours after a ortic coarctation. Mean carotid blood pressures and the carotid-femora l artery blood pressure gradients were not different among coarctation , coarctation plus DuP 753, and coarctation plus PD 123319 animals. Ho wever, ratios of heart weight to body weight were higher in coarctatio n (4.95 +/- 0.8) or coarctation plus PD 123319 (4.52 +/- 0.5) than in sham animals (3.6 +/- 0.4; P < .005 and .05, respectively). In coarcta tion plus DuP 753-treated animals heart weight-body weight ratios were not different from sham or sham plus DuP 753 animals (3.9 +/- 0.4 ver sus 3.61 +/- 0.4 or 3.3 +/- 0.08, respectively). Type 1 receptor mRNA levels were significantly increased in the coarctation group, with the highest levels in the coarctation plus DuP 753 and sham plus DuP 753 groups. To determine whether growth factors were involved in the hyper trophic process, we measured transforming growth factor-beta(1) mRNA l evels. Northern analysis demonstrated a twofold increase in coarctatio n animals compared with sham or coarctation plus DuP 753-treated anima ls. Therefore, cardiac hypertrophy induced by abdominal coarctation of the aorta is mediated by the angiotensin type 1 receptor and results in upregulation of the cardiac angiotensin type 1 and transforming gro wth factor-beta(1) genes.