Combined exposure to cigarette smoke and hypercholesterolemia decreases vasorelaxation of the aorta

Purpose: The purpose of this study was to determine the physiologic effects of cigarette smoke exposure and dietary cholesterol on the availability of nitric oxide in aortic vascular rings. Methods: Four groups of New Zealand White rabbits were placed in an air flow chamber for 3 hours per day for 8 weeks. Two of these groups were exposed to smoke from 600 cigarettes per day 5 days a week added to the chamber inflow by a robotic smoke generator. One of these groups was made hypercholesterolemic by being fed a 0.3% cholesterol diet. Two groups of rabbits were similarly placed in the air flow chamber but without smoke exposure, of which one group was also made hypercholesterolemic. After an 8-week period, the rabbits were killed and the infrarenal aortas were excised. The vessels were cut into 3 mm rings and suspended from tension transducers. The rings were contracted with potassium chloride to determine vessel integrity. Then one ring from each aorta was maximally contracted with norepinephrine, and the experimental ring was contracted to 50% of maximum. Relaxation of the rings in response to incremental doses of acetylcholine was measured. Results: No significant differences were seen in contraction to potassium chloride or norepinephrine in any group. A significant decrease in acetylcholine-mediated relaxation was seen only in the smoke-exposed, cholesterol-fed group. Conclusions: Endothelial damage, as measured by acetylcholine-mediated vasorelaxation, occurs in the infrarenal aorta in rabbits that are exposed to both cigarette smoke and elevated dietary cholesterol. Cigarette smoke exposure alone or hypercholesterolemia alone in this model did not result in significant alteration in acetylcholine-mediated vasorelaxation.