Nicotine decreases the porosity of the rat liver sieve: a possible mechanism for hypercholesterolaemia.

Nicotine was fed to rats for 6 weeks, as a weight adjusted dose equivalent to that of a human being smoking 50 to 100 cigarettes per day. Those rats fed nicotine developed hypercholesterolaemia. Scanning electron microscopy showed the porosity of the hepatic sinusoidal endothelium of nicotine fed animals was about 40% that of control animals. The decline in porosity was found to be due to a reduction in diameter rather than number of fenestrae. We believe that this decreased hepatic sinusoidal porosity may alter cholesterol homeostasis by increasing the circulation time of chylomicron remnants too large to pass through the fenestrae. This phenomenon may be an aetiological factor in the known correlation between cigarette smoking, atherosclerosis, and coronary heart disease in humans.