Long-term nicotine exposure increases aortic endothelial cell death and enhances transendothelial macromolecular transport in rats.
Repeated endothelial cell injury has been suggested as an initiating factor in atherogenesis. Dying or dead endothelial cells have been shown to make significant contributions to the local enhancement of transendothelial macromolecular transport. Since cigarette smoking is one of the major risk factors for atherosclerosis, we examined the hypothesis that smoking accelerates atherogenesis by increasing the frequency of endothelial cell death and hence transendothelial macromolecular transport. Sixteen male Sprague-Dawley rats were given nicotine at a weight-adjusted dose of 5 mg/kg body wt per day in their drinking water over a period of 6 weeks. A group of 16 age-matched male Sprague-Dawley rats not exposed to nicotine and maintained over the same time period served as the control group. In en face preparations of thoracic aorta, immunoglobulin G-containing dying or dead endothelial cells were identified by the indirect immunoperoxidase method, and endothelial leakage to Evans blue-albumin (EBA) complexes (5 minutes after intravenous injection) was visualized by fluorescence microscopy. The results showed that in nicotine-treated rats, 51% of dead endothelial cells were associated with EBA leakage, which was responsible for 57% of total EBA leaky foci. Both the frequency of endothelial cell death (0.94 +/- 0.11% versus 0.40 +/- 0.04%, p < 0.0001 by two-tailed, unpaired Student's t test) and the number density of EBA leaky foci (6.45 +/- 1.23/mm2 versus 3.30 +/- 0.49/mm2, p < 0.05 by two-tailed, unpaired t test) were significantly greater in nicotine-treated rats than in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Lin
S J
SJ
Department of Medicine, Taipei Veterans General Hospital, Taiwan, ROC.
Hong
C Y
CY
Chang
M S
MS
Chiang
B N
BN
Chien
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001692:Biological Transport / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005070:Evans Blue / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000097:blood / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism
D012709:Serum Albumin; D005070:Evans Blue; D009538:Nicotine