Contrast medium- and mannitol-induced apoptosis in heart and kidney of SHRrats

The induction of apoptosis by contrast media (CM) and mannitol (M) was inve stigated in the hearts and kidneys of 12-mo-old male SHR rats. Ten groups o f 3 SHR rats received a dose of 5 ml/kg of one of the following: Hypaque (H )-30, H-60, H-76, Omnipaque (O)-140, O-350, mannitol (M)-4%, M-9%, M-19%, M -27%, or saline (S). DNA fragmentation was detected using the terminal deox ynucleotidyl transferase-mediated [TdT] dUTP nick-end labeling (TUNEL) meth od, and the morphology characteristics of apoptosis were confirmed in cardi ac and renal cells. The immunoreactivities of Bcl-2, Bar, and p53 were asse ssed immunohistochemically in the kidneys. Apoptosis occurred in cardiac my ocytes and renal tubular and glomerular cells as well as in vascular endoth elial and smooth muscle cells of the heart and kidneys. The high frequency of apoptosis correlated significantly with the increase in the osmolality o f the H, O, and hi. The increased Bax, the increased p53, and the decreased Bcl-2 immunoreactivities were detected in H- or O-treated, but not in M-tr eated, rats. These findings suggest that CM and M activate cardiac and rena l apoptosis by different mechanisms and that the apoptotic process may be i mplicated in acute heart and renal damage.