The effects of alpha-methyldopa on cardiac hypertrophy in spontaneously hypertensive rats: ultrastructural, stereological, and morphometric analysis

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Abstract
This study examined the role of α-methyldopa on the myocardial cell (cardiocyte) and its microvascular bed. Spontaneously hypertensive rats (SHR) were administered the drug commencing at 4 weeks of age. Tissue specimens from perfused-fixed hearts of 16 week-old rats were studied by electron microscopy and data obtained using stereological and morphometric methods. In both the subendocardium and subepicardium of SHR cardiocytes were hypertrophic and a significant drop in capillary density was evident. In spite of the failure of α-methyldopa (in the protocol used in this study) to significantly reduce blood pressure in SHR, heart weight values of the drug-treated rats (T-SHR) were in the high normal range. Cardiocytes comprising the subepicardium were similar in size to those of normotensive animals, while those comprising the subendocardium were mildly hypertrophic. While hypertrophy in the SHR was associated with a decrease in the cellular fraction of mitochondrial volume and a decrease in the volume ratio: mitochondria/myofibrils, in T-SHR these parameters were normal even in cells from the mildly hypertrophic sub- endocardial region. Enhanced folding of the intercalated disc, though variable, was found to be most common in both the subepicardium and subendocardium of T-SHR. These data suggest that α-methyldopa may prevent or modify hypertrophy without significantly altering blood pressure. While certain cellular parameters, ie, fractional volumes of mitochondria and myofibrils, may be normalised by this intervention, enhanced folding of the intercalated disc is accentuated.