Katayama S, Abe M, Inaba M, Itabashi A, Ishii J
Fourth Department of Medicine, Saitama Medical School, Japan.
Jpn Heart J. 1993 Nov;34(6):773-83. doi: 10.1536/ihj.34.773.
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.
一项研究旨在阐明卡托普利（CAP）或尼群地平（NITR）对自发性高血压大鼠（SHR）心脏肥大以及层粘连蛋白B2或胶原蛋白（COL）基因在左心室表达的影响。20周龄的SHR心脏重量显著增加。通过Northern印迹分析测定，Wistar-Kyoto大鼠和SHR中IV型COLα1链的基因表达随年龄降低。两种品系的左心室层粘连蛋白B2 mRNA在12周时降低，在20周时再次升高。从8周到20周，每天给SHR口服CAP（40 mg/kg，n = 5）或NITR（30 mg/kg，n = 4）可使血压降至142 mmHg（与对照组197 mmHg相比，p < 0.01，n = 5）。对照组心脏重量为1.26±0.04（SE）g，CAP可将其降至1.03±0.05 g（p < 0.01），但NITR不能（1.24±0.04）。CAP和NITR分别将左心室层粘连蛋白B2基因表达减弱至对照值的41%和32%。CAP显著降低左心室IV型COLα1 mRNA至对照水平的11%，而NITR仅使其降低至75%。CAP还降低了I型COLα1或α2 mRNA。这些结果表明，血管紧张素转换酶抑制剂通过抑制细胞外基质的基因表达来预防和/或导致心脏肥大的消退，并且血管紧张素II可能在心脏肥大中起关键作用。
