Key result
Captopril significantly reduced cardiac weight to 1.03g compared to 1.26g in controls (p<0.01) and decreased type IV collagen mRNA to 11% of control levels in spontaneously hypertensive rats.
Why the study?
Does captopril or nitrendipine prevent cardiac hypertrophy and alter left ventricular extracellular matrix gene expression in spontaneously hypertensive rats?
Does captopril or nitrendipine prevent cardiac hypertrophy and alter left ventricular extracellular matrix gene expression in spontaneously hypertensive rats?
Absolute Event Rate: 1.03% vs 1.26%
p-value: p=<0.01
ACE inhibitors, but not calcium channel blockers, prevent cardiac hypertrophy in spontaneously hypertensive rats by inhibiting extracellular matrix gene expression, suggesting a blood pressure-independent role of angiotensin II.
ACE inhibitors may attenuate hypertrophy via ECM modulation in rat models; leaves open human translation.
A study was designed to clarify the effects of captopril (CAP) or nitrendipine (NITR) on cardiac hypertrophy and left ventricular expression of the laminin B2 or collagen (COL) gene in spontaneously hypertensive rats (SHRs). Cardiac weight was significantly increased in 20-week-old SHRs. Gene expression of the alpha 1 chain of type IV COL determined by northern blot analysis decreased with age in Wistar-Kyoto rats and SHRs. Left ventricular laminin B2 mRNA was decreased at 12 weeks and increased again at 20 weeks in both strains. Daily oral administration of CAP (40 mg/kg, n = 5) or NITR (30 mg/kg, n = 4) to SHRs from 8 to 20 weeks decreased blood pressure to 142 mmHg (p < 0.01 vs 197 mmHg in controls, n = 5). Cardiac weight was 1.26 +/- 0.04 (SE) g in controls and was reduced to 1.03 +/- 0.05 g (p < 0.01) by CAP, but not by NITR (1.24 +/- 0.04). Left ventricular laminin B2 gene expression was attenuated by CAP and NITR to 41% and 32% of the control value, respectively. CAP significantly decreased left ventricular alpha 1 type IV COL mRNA to 11% of the control level, whereas NITR caused a reduction only to 75%. CAP also decreased alpha 1 or alpha 2 type I COL mRNA. These results suggest that angiotensin converting enzyme inhibitors prevent and/or cause regression of cardiac hypertrophy by inhibiting the gene expression of extracellular matrix, and that angiotensin II may have a pivotal role in cardiac hypertrophy.
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Katayama et al. (1993) studied Cardiac hypertrophy in spontaneously hypertensive rats (n=14). Captopril vs. Vehicle control was evaluated on Cardiac weight (g) (p=<0.01). Captopril significantly reduced cardiac weight to 1.03g compared to 1.26g in controls (p<0.01) and decreased type IV collagen mRNA to 11% of control levels in spontaneously hypertensive rats.
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