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.