Ultrastructural changes during myocardial hypertrophy and its regression: Long-term effects of nifedipine in adult spontaneously hypertensive rats

Nifedipine (20mg/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±13mmHg). 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.