INCREASED PREVALENCE OF AORTIC FATTY STREAKS IN CHOLESTEROL-FED RABBITS ADMINISTERED INTRAVENOUS COCAINE - THE ROLE OF VASCULAR ENDOTHELIUM

Several recent postmortem studies suggest an increased prevalence of a therosclerosis in young habitual cocaine abusers. However, little is k nown about the effects of cocaine abuse on the vascular endothelium an d its relationship to atherosclerosis. Therefore, the consequence of c hronic administration of intravenous cocaine on the induction of aorti c sudanophilia was examined. Male New Zealand White rabbits were fed a 0.5% cholesterol diet for 10 wk. During this per-iod, animals were ra ndomized to receive either cocaine-hydrochloride (0.25 mg/kg) intraven ously (n = 17) twice daily; or an equivalent volume of 0.9% physiologi c saline, control group (n = 16). Mean values for total circulating le ukocytes and platelets and total plasma cholesterol and triglycerides were similar in both groups throughout the protocol. At the completion of the study, aortic sudanophilia was measured and expressed as a per centage of regional involvement (R1 = proximal 4 cm, R2 = middle 6 cm, and R3 = distal 10 cm). Statistical significance among groups was ach ieved in the proximal thoracic aorta (p = 0.057). No significant diffe rences in sudanophilia were noted in the middle and distal segments. W hen animals were placed in subgroups according to percent total plaque involvement, there was a significant increased distribution of rabbit s with a greater extent of sudanophilia in the cocaine-treated group a s compared with control (p = 0.01, chi-square analysis). Immunocytoche mical studies using the macrophage-specific and muscle actin-specific monoclonal antibodies demonstrated that sudanophilic areas in both gro ups were predominantly composed of macrophage-derived foam cells. Eval uation of plaque morphology showed an increase in intimal plaque thick ness and in the number of macrophages and smooth muscle cells in cocai ne-treated animals; however, group differences were not statistically significant. Because no significant differences were found in the cell ular composition of atherosclerotic plaques between groups, further st udies were performed to assess the effects of cocaine on the permeabil ity function of cultured endothelial cell monolayers as a possible mec hanism of increased sudanophilia. Cocaine (100 muM)-treated endothelia l cell monolayers demonstrated an increased permeability to horseradis h peroxidase during all time intervals studied (0-6 hr). Permeability differences were statistically significant at 30 min and 1 hr (p = 0.0 03 and 0.02, respectively). Collectively, these observations suggest t hat administration of cocaine to cholesterol-fed rabbits increases the prevalence of aortic sudanophilia via at least one possible mechanism involving enhanced vascular permeability.