Regression of Neointimal Lesions in the Carotid Artery of Nifedipine-Treated SHR and WKY Rats: Possible Role of Apoptosis

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Abstract
We previously observed that nifedipine reduces aortic hypertrophy in spontaneously hypertensive rats (SHR) partly by inducing smooth muscle cell (SMC) apoptosis. The present study examined nifedipine regulation of SMC apoptosis in carotids with or without a neointima. A neointima was produced by endothelial denudation of the left carotid of SHR and WKY rats. The contralateral carotid remained uninjured. Beginning at week 6 after injury, rats received nifedipine or placebo for 5 and 7 additional weeks. In situ terminal deoxynucleotidyl transferase (TdT)-mediated DNA labeling was used to mark apoptotic nuclei. Nifedipine reduced blood pressure in SHR but not WKY rats. Nifedipine had antihypertrophic effects in both SHR and WKY rats. In each strain, the greater reduction in cross-sectional area was seen in the neointima. In this tissue, nifedipine significantly increased TdT-positive SMC (4-fold at week 5 in SHR and 5-fold at week 7 in WKY rats) and reduced SMC number (70% in SHR and 29% in WKY rats) at week 7 compared to week 0. The effects were less pronounced in the injured and uninjured media. Thus, the antihypertrophic action of nifedipine is amplified in the neointima of SHR and WKY rat carotids, where histological evidence suggests SMC deletion via apoptosis.