Cigarette smoke extract contracts isolated porcine coronary arteries by superoxide anion-mediated degradation of EDRF.
To test whether cigarette smoke extract (CSE) influences the endothelial regulation of vascular tone in vitro, pig coronary arterial rings were incubated in organ chambers and isometric tension changes were examined. CSE was prepared by bubbling mainstream smoke of one filter cigarette into phosphate-buffered saline (2 ml). Fresh CSE (3.3, 10, and 30 microliters/ml) elicited initial contraction and subsequent relaxation during stable contraction to prostaglandin F2 alpha (PGF2 alpha). Initial contraction to CSE was dependent on the presence of endothelium, whereas subsequent relaxation was endothelium independent. Initial contraction was significantly attenuated by superoxide dismutase (SOD), methylene blue, but not by catalase. Prior inhibition of the basal release of endothelium-derived relaxing factor by NG-monomethyl-L-arginine also inhibited the initial contraction, and this inhibition was reversed by coincubation with L-arginine but not D-arginine. Subsequent relaxation was significantly potentiated by SOD but was markedly attenuated by methylene blue. CSE reduced ferricytochrome c, and this reduction was significantly inhibited by SOD. In conclusion, CSE induced biphasic tension change, initial contraction, and subsequent relaxation during stable contraction to PGF2 alpha in isolated pig coronary arteries. The initial contraction may be, at least in part, mediated through the degradation of basally released endothelium-derived relaxing factor (nitric oxide) by superoxide anions derived from CSE.
Murohara
T
T
Division of Cardiology, Kumamoto University School of Medicine, Japan.
Kugiyama
K
K
Ohgushi
M
M
Sugiyama
S
S
Yasue
H
H
D000818:Animals; D000838:Anions / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries; D000001:Calcimycin / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology*; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008751:Methylene Blue / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D012906:Smoke; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013552:Swine; D014661:Vasoconstriction; D019323:omega-N-Methylarginine
D000838:Anions; D012906:Smoke; D013481:Superoxides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000001:Calcimycin; D009538:Nicotine; D001120:Arginine; D002374:Catalase; D013482:Superoxide Dismutase; D008751:Methylene Blue