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Objective: To assess the effects of rhBNP on left ventricular (LV) remodeling in rats with acute myocardial infarction (AMI)., Methods: AMI was induced by ligating coronary artery in male Sprague Dawley rats. Two days after surgery, AMI rats received intravenous infusion of rhBNP (15 microg/kg or 5 microg/kg once daily, n = 15 each) or saline (placebo control, n = 15) through Jugular Vein. Sham-operated rats (n = 15) served as normal control. Four weeks later, hemodynamic measurements were performed, left ventricular weight (LVW), ratio of left ventricular weight to body weight (LVW/BW), left ventricular diameter (LVD) and infarct size were determined. Plasma angiotensin II and myocardial angiotensin II levels were also measured., Results: Compared with sham-operated rats, LVW, LVW/BW, LVD and myocardial angiotensin II level were significantly increased, while the LV systolic pressure (LVSP), +/- dp/dt were significantly reduced in saline treated AMI rats (all P < 0.05). LVW/BW, MI size, LVD and myocardial angiotensin II in rhBNP treated AMI rats were significantly lower [LVW: (492.6 +/- 34.0) mg, (498.8 +/- 47.8) mg, (570.0 +/- 24.2) mg, P < 0.01; LVW/BW: 2.0 +/- 0.2, 2.0 +/- 0.2, 2.3 +/- 0.1, P < 0.01; LVD: (25.3 +/- 2.9)%, (31.4 +/- 3.0)%, (46.4 +/- 3.0)%, P < 0.01; myocardial angiotensin II: (881.3 +/- 62.7) pg/L, (1186.0 +/- 94.5) pg/L, (2436.7 +/- 280.3) pg/L, P < 0.05], while LVSP and +/- dp/dt in rhBNP treatment groups were significantly increased than saline treated AMI rats (P < 0.05 or P < 0.01)., Conclusion: RhBNP is effective in attenuating left ventricular remodeling after AMI in rats.

Objective: To investigate the effects of angiotensin-(1-7) on remodeling of myocardial collagen network in pressure-overloaded rats., Methods: A rat model of pressure-overloaded heart was induced by constriction of abdominal aorta. Seventy-five male Sprague Dawley rats were randomized to sham-operated group, model control group and angiotensin-(1-7) group. The rats of the latter two groups were treated with intravenous infusion of either angiotensin-(1-7) (25 microg x kg(-1) x h(-1)) or saline after operation. Ratio of left ventricular weight to body weight (LVW/BW) and myocardial collagen volume fraction (CVF) were determined at 1 and 4 weeks after operation. And types I and III collagen mRNA expressions were assessed with reverse transcription-polymerase chain reaction (RT-PCR)., Results: At 1 week after the operation, types I and III collagen mRNA expressions of the left ventricular myocardium in model group and angiotensin-(1-7) group were increased significantly compared with those in sham-operated group. But those in angiotensin-(1-7) group were significantly lower than that in model group. At 4 weeks after the operation, LVW/BW and CVF were increased significantly in model group and angiotension-(1-7) group compared with those in sham-operated group, but those in angiotension-(1-7) group were significantly lower than that of model group., Conclusion: Angiotensin -(1-7) can attenuate remodeling of myocardial collagen network in pressure-overloaded rats.

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 μg/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 [3H] incorporation were measured. Transforming growth factor (TGF)-β1 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-β1 and downregulation of smad7 mRNA and protein expression. The in vitro experiments further proved that BNP inhibited cardiac hypertrophy and changes in the TGF-β1/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-β1 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. [ABSTRACT FROM AUTHOR]