Kimpara T, Okabe M, Nishimura H, Hayashi T, Imamura K, Kawamura K
Department of Internal Medicine, Osaka Medical College, Japan.
Heart Vessels. 1997;12(3):143-51. doi: 10.1007/BF02767132.
Nifedipine (20 mg/kg/day) was given to 15-week-old spontaneously hypertensive rats for 20 weeks (SHR-N, n = 8). Comparison was done with sex-matched 15-week-old SHR (SHR-15, n = 7), untreated 35-week-old SHR (SHR-C, n = 10), 15-week-old normotensive Wistar-Kyoto rats (WKY-15, n = 15), and 35-week-old WKY (WKY-15, n = 5). Light and electron microscopic data on the subepicardial, middle and subendocardial layers and papillary muscles of the left ventricle were compared among the five rat groups. In SHR-N, blood pressure was significantly reduced by nifedipine, but was higher than in WKY-35 (199 +/- 11 mmHg vs 121 +/- 13 mmHg). The left ventricular weight/body weight ratio was much lower in SHR-N than in SHR-C, and was even below the baseline value in SHR-15. In addition, cardiac myocyte diameter was much smaller in each myocardial layer of SHR-N than in SHR-C, and was similar to the findings in SHR-15, but still larger than in WKY-35. The interstitial area ratio was markedly reduced in SHR-N and did not differ from that in SHR-15 or even WKY-15, while capillary density was significantly greater than in SHR-C and comparable to that in WKY-35. In SHR-C, large fibrotic foci were common, and many hypertrophic cardiac myocytes showed various degenerative changes including those of mitochondria and widening of the intermyofibrillar spaces. These changes were rarely seen in SHR-N. The intracellular volume ratio of myofibrils did not differ between SHR-N and WKY-35, but was significantly decreased in SHR-C, whereas that of mitochondria did not differ between SHR-N and SHR-C or WKY-35. These findings indicate that despite only a moderate suppression of hypertension, long-term nifedipine treatment caused regression of left ventricular hypertrophy, with cardiocyte hypertrophy, interstitial fibrosis, degenerative changes, and subcellular remodeling being reversed to the baseline levels in SHR-15. In addition, the capillary density was increased to that seen in WKY-35.
将硝苯地平（20毫克/千克/天）给予15周龄的自发性高血压大鼠，持续给药20周（SHR-N，n = 8）。与性别匹配的15周龄SHR（SHR-15，n = 7）、未治疗的35周龄SHR（SHR-C，n = 10）、15周龄的正常血压Wistar-Kyoto大鼠（WKY-15，n = 15）以及35周龄的WKY（WKY-35，n = 5）进行比较。比较了五个大鼠组左心室心外膜下层、中层、心内膜下层以及乳头肌的光镜和电镜数据。在SHR-N组中，硝苯地平使血压显著降低，但仍高于WKY-35组（199±11毫米汞柱对121±13毫米汞柱）。SHR-N组的左心室重量/体重比远低于SHR-C组，甚至低于SHR-15组的基线值。此外，SHR-N组各心肌层的心肌细胞直径均远小于SHR-C组，与SHR-15组的结果相似，但仍大于WKY-35组。SHR-N组的间质面积比显著降低，与SHR-15组甚至WKY-15组无差异，而毛细血管密度显著高于SHR-C组，与WKY-35组相当。在SHR-C组中，常见大的纤维化病灶，许多肥大的心肌细胞出现各种退行性改变，包括线粒体改变和肌原纤维间隙增宽。这些改变在SHR-N组中很少见。SHR-N组和WKY-35组肌原纤维的细胞内体积比无差异，但SHR-C组显著降低，而线粒体的细胞内体积比在SHR-N组、SHR-C组和WKY-35组之间无差异。这些发现表明，尽管硝苯地平仅适度抑制高血压，但长期治疗可使左心室肥厚消退，心肌细胞肥大、间质纤维化、退行性改变和亚细胞重塑恢复到SHR-15组的基线水平。此外，毛细血管密度增加到WKY-35组的水平。
