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K. Li, J. H. Wang, I. Hale, H. J. Ward, P-686: Cocaine-induced cytopathy and apoptosis of vascular smooth muscle cells from spontaneous hypertensive rats, American Journal of Hypertension, Volume 14, Issue S1, April 2001, Page 259A, https://doi.org/10.1016/S0895-7061(01)02016-7
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Abstract
There is increasing clinical evidence to document cocaine abuse as a risk factor for progressive cardio-renal disease, especially in hypertensive individuals. The present study was designed to define the vasculotoxic and nephrotoxic effects of cocaine at the cellular level. The smooth muscle cells were isolated from the aorta of 8-week old spontaneous hypertensive rats. Cultured vascular smooth muscle cells at passages between 8 and 10 were exposed to cocaine concentrations ranging from 0.1 μ M to 1 mM for 24 and 72 hours. At a cocaine concentration of 0.1 mM, phase contrast microscopy revealed cytoplasmic vacuolization after 24-hour incubation. The highest cocaine concentration of 1 mM was associated with the development of early apoptotic changes of cell retraction and chromatin condensation. Chromatin condensation was also detected as bright fluorescent staining of DNA by Hoechst 35228, distributed as a granular pattern in the nucleus or as apoptotic bodies. Prolonged (72 hours) cocaine exposure was accompanied by nuclear shrinkage and cell detachment. The apoptotic effect of cocaine on vascular smooth muscle cells was further confirmed by DNA fragmentation using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. After 24-hour incubation with cocaine, positive TUNEL stained cells were observed at the concentration of 1 mM. In vascular smooth muscle cells exposed to cocaine for 72 hours, TUNEL assay showed a dose-dependent apoptotic effect at concentrations of 0.03 mM and higher. These direct cytopathic changes and the pro-apoptotic effects of cocaine support the clinical observations of increased cardio-renal morbidity in cocaine abuser.
