1. Previously, we showed that long-term treatment of rats after
myocardial infarction (MI) with
B-type natriuretic peptide (BNP) prevented ventricular remodelling. However, it is unclear whether long-term BNP treatment affects
cardiac hypertrophy and, if so, its mechanism of action. In the present study, we investigated the effects of long-term BNP treatment on
cardiac hypertrophy and the molecular mechanisms involved. 2.
Cardiac hypertrophy was established in rats by
ligation of the left anterior descending coronary artery.
After treatment with BNP (5 or 15 microg/kg per day) for 8 weeks, indices of
cardiac hypertrophy were determined. In separate in vitro experiments, cardiomyocyte
hypertrophy was induced by treatment of cardiomyocytes with 10(-6) mol/L
angiotensin (Ang) II for 48 h and cell surface area and [(3)H] incorporation were measured.
Transforming growth factor (TGF)-beta1 and smad7
mRNA and
protein expression in vivo and in vitro were detected using reverse transcription-polymerase chain reaction and western blotting. 3. Long-term BNP treatment dose-dependently attenuated
cardiac hypertrophy and improved cardiac function in rats after MI. Furthermore, BNP attenuated the upregulation of
TGF-beta1 and downregulation of smad7
mRNA and
protein expression. The in vitro experiments further proved that BNP inhibited
cardiac hypertrophy and changes in the TGF-beta1/smad7 pathway, which were completely blocked by the
cyclic GMP-dependent protein kinase (PKG) inhibitor,
KT5823 (cells were treated with 10(-6) mol/L
KT5823 for 48 h). 4. The results of the present study demonstrate that long-term treatment of rats with BNP dose-dependently attenuates
cardiac hypertrophy and that this is associated with downregulation of
TGF-beta1 and upregulation of smad7 via PKG signalling. Long-term BNP treatment may be a new therapeutic strategy to prevent
cardiac hypertrophy and progression to
heart failure.