Activation of the renin-angiotensin system (RAS) contributes substantially to cardiac remodelling. As we have shown in ventricular cardiomyocytes of adult rat, angiotensin II enhances hypertrophic growth, apoptosis and contributes to contractile dysfunction in these cells. The aim of this study was, to analyse hypertrophy-, apoptosis- and contraction-relevant gene expression in a mouse model with activated RAS system after unilateral renal artery stenosis (2K1C). In 4 - 5 week old mice renal artery of one kidney was clipped (2K1C). As control sham operated animals were used (sham). Within 4 weeks after stenosis blood pressure in 2K1C mice increased from 121.1 ± 7.3 mmHg to 142.5 ± 4.0 mmHg (p<0.05 vs. sham, n=16). As signs for hypertrophic cardiac growth, heart/body weight was increased to 111.6 ± 3.4 % (p<0.05 vs. sham, n=16), and BNP-mRNA expression was elevated 6.0 ± 2.5 - 24.8 fold (p<0.05 vs. sham, n=6). Also a slight, but non-significant 1.8-fold enhancement in ANP-mRNA expression was observed. Concerning contraction-relevant gene expression a 0.13 ± 0.05 - 0.32 fold downregulation of SERCA-mRNA was found (p<0.05 vs. sham, n=5), while mRNA of phospholamban increased slightly by 2.0 ± 1.1 - 3.7 fold (n.s. vs. sham, n=5). mRNA of the growth factor TGFb1 was elevated 3.4 ± 1.5 - 7.4 fold (p<0.05 vs. Sham, n=6). At the same time, mRNA of SMAD7, which is an inhibitory protein of TGFb1-signaling, was enhanced 5.4 ± 2.0 - 17.2 fold (p<0.05 vs. sham, n=5). Changes in mRNA expression of apoptotic genes like Bcl-2 or Bax were not present.

Conclusions: 

4 weeks after unilateral renal artery stenosis mice develop moderate hypertrophic cardiac growth with a reduction in mRNA expression of the calcium pump SERCA, which may reduce cardiac contractile function. Induction of TGFb1 goes a along with enhanced expression of SMAD7, indicating inhibition of the TGFb1 signalling pathway. Therefore, TGFb may not exert its detrimental effects like apoptosis induction under these conditions.