Connective tissue growth factor (CTGF) is a secreted
protein that regulates
fibrosis. We hypothesized that CTGF is induced in a pressure-overloaded (PO) heart and that blocking the
angiotensin II type 1 receptor would reduce CTGF expression. Accordingly, we administered
olmesartan and compared its effects with other
antihypertensive drugs in a PO heart. CTGF induction was determined in a rat PO model, and
olmesartan,
hydralazine or saline was continuously administered. The effects of
olmesartan on CTGF induction, myocyte
hypertrophy and
fibrosis were evaluated. The effect of
olmesartan on cardiac function was also examined in CTGF- and
transforming growth factor-beta 1 (TGF-β1)-infused rats. CTGF was increased in the PO heart 3 days after aortic banding and was markedly distributed around the perivascular fibrotic area. After 28 days, blood pressure was not significantly different in the
olmesartan and
hydralazine groups, but
olmesartan treatment reduced CTGF distribution in PO hearts.
Olmesartan was associated with a significantly reduced myocyte
hypertrophy index (4.77±0.48 for
olmesartan and 6.05±1.45 for saline, P<0.01),
fibrosis area (32.0±15.5% compared with the saline group, P<0.05) and serum TGF-β1 level (62.6±10.6 ng ml⁻¹ for
olmesartan and 84.4±7.2 ng ml⁻¹ for
hydralazine, P<0.05). In addition, cardiac function was significantly preserved in the
olmesartan group compared with the saline group. Finally,
olmesartan ameliorated the cardiac dysfunction in CTGF- and TGF-β1-infused rats.
Olmesartan attenuated CTGF induction, reduced perivascular
fibrosis and ameliorated cardiac dysfunction in a PO heart. Our results provide insight into the beneficial effects of
olmesartan on PO hearts, independent of blood-pressure lowering.