Supersensitivity of atherosclerotic artery to constrictor effect of cigarette smoke extract.
OBJECTIVE
The aim of this study was to assess whether contractile response of arteries to aqueous component of cigarette smoke extract (CSE) may be modulated in atherosclerotic arteries.


METHODS
Thoracic aortas were isolated from control rabbits and from 1.5% cholesterol-fed rabbits, all of which had visible advanced atheromatous surface changes on the aortas. CSE was prepared by bubbling main stream of smoke from one cigarette with filter into 2 ml of phosphate-buffered saline. The thoracic aortic rings were suspended in organ chambers and tested with CSE (0.01-3.0 microliters/ml buffer in the organ chamber) after precontraction with 0.1 mumol/l of phenylephrine (PE).


RESULTS
The contractile response to CSE was significantly greater in atherosclerotic aortas than in control aortas (the maximal contraction expressed as % of the precontraction; control aortas 10.8 +/- 2.8%, atherosclerotic aortas 42.6 +/- 4.7%; P < 0.01). The magnitude of the precontractions by PE was not different between control and atherosclerotic aortas. Exogenous addition of superoxide dismutase (SOD) significantly attenuated the CSE-induced contraction in both control and atherosclerotic aortas and pretreatment of aortic rings with diethyldithiocarbamate to deplete of endogenous vascular CuZn-SOD activity potentiated the CSE-induced contraction in control aortas, while it had no significant effect in atherosclerotic aortas. The vascular SOD activity was significantly lower in atherosclerotic aortas than in control aortas ((U/mg protein): control aortas 38.2 +/- 3.3, atherosclerotic aortas 18.5 +/- 2.4; P < 0.01).


CONCLUSIONS
These results indicate that atherosclerotic arteries may be supersensitive to the constrictor effect of superoxide anion derived from CSE. The decrease in endogenous vascular SOD activity may partly contribute to the increased susceptibility to oxidative stress in atherosclerotic arteries.
Department of Medicine, Kumamoto University School of Medicine, Japan. kiyo@gpo.kumamoto-u.ac.jp
S
S
Sugiyama
K
K
Kugiyama
M
M
Ohgushi
T
T
Matsumura
Y
Y
Ota
H
H
Doi
N
N
Ogata
H
H
Oka
H
H
Yasue
D000818:Animals; D001158:Arteries; D001161:Arteriosclerosis / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010947:Plants, Toxic; D011817:Rabbits; D012906:Smoke; D013482:Superoxide Dismutase / Q000494:pharmacology; D014026:Nicotiana; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D012906:Smoke; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D013482:Superoxide Dismutase