Is apoptosis present in progression to chronic hypertensive heart failure?

Background: Cardiomyocyte apoptosis is believed to occur in hypertension. Isolated myocyte data from spontaneously hypertensive heart failure (SHHF) rats, however, suggest that significant myocyte loss does not occur in this model. To investigate this issue further, heart sections from failing and nonfailing SHHF rats were examined by using in situ terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling (TUNEL). Additional hearts were optimally fixed by perfusion with glutaraldehyde and histologically examined for evidence of myocyte damage or loss. Methods and Results: Five Sprague-Dawley (SD) rats, 8 failing SHHF rats, and 6 nonfailing SHHF rats were perfusion-fixed with formaldehyde and used for TUNEL assay. Heart sections from each group were also treated with DNase for positive controls. There were no significant differences in the number of TUNEL-positive cells in SD, failing SHHF, and nonfailing SHHF rats. Additionally, extensive screening of 1-mu m sections of optimally fixed failing hearts revealed little evidence of myocyte loss or nuclear characteristics suggestive of apoptosis. Conclusion: Apoptosis does not appear to be an important component of myocardial remodeling in SHHF rats during hypertrophy or end-stage heart failure. Examination of myocyte nuclear structure by high-resolution microscopy of optimally fixed tissues is recommended as an alternative approach to study apoptosis.