Regression of neointimal lesions in the carotid artery of nifedipine-treated SHR and WKY rats: Possible role of apoptosis

We previously observed that nifedipine reduces aortic hypertrophy in sponta neously hypertensive rats (SHR) partly by inducing, smooth muscle cell (SMC ) apoptosis. The present study examined nifedipine regulation of SMC apopto sis in carotids with or without a neointima. A neointima was produced by en dothelial denudation of the left carotid of SHR and WKY rats. The contralat eral carotid remained uninjured. Beginning at week 6 after injury, rats rec eived nifedipine or placebo for 5 and 7 additional weeks. In situ terminal deoxynucleotidyl transferase (TdT)-mediated DNA labeling was used to mark a poptotic 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 neoi ntima. 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 e ffects were less pronounced in the injured and uninjured media. Thus, the a ntihypertrophic action of nifedipine is amplified in the neointima of SHR a nd WKY rat carotids, where histological evidence suggests SMC deletion via apoptosis. Copyright (C) 2001 S. Karger AG, Basel.