Impairment of endothelium-dependent relaxation of rabbit aortas by cigarette smoke extract--role of free radicals and attenuation by captopril.
The aim of this study was to examine the effects of the water soluble component of cigarette smoke extract (CSE) on endothelium-dependent relaxation (EDR) of isolated rabbit aortas. The incubation with CSE was found to inhibit EDR in a dose-dependent manner. Co-incubation of the aortic strips with superoxide dismutase (SOD), N-acetylcysteine, glutathione or dimethyl sulfoxide (DMSO), free radical scavengers, attenuated the CSE-induced inhibition of the arterial relaxation. Co-incubation of the strips with captopril (3 mM), an angiotensin converting enzyme inhibitor, also attenuated CSE-induced impairment of vasorelaxation. In parallel experiments using cultured human endothelial cells, CSE suppressed endothelial release of NOx, stable metabolites of nitric oxide (NO). SOD, DMSO and captopril attenuated the suppression of NO production by CSE in association with reduction of free radicals, superoxide anions and hydroxyl radicals, in CSE solution. Neither lactate dehydrogenase release from the cultured endothelial cells nor cell death estimated by trypan blue exclusion test was found after the incubation of the cultured endothelial cells with CSE. The results indicate that free radicals in CSE induce the impairment of EDR, which may be partly due to suppression of NO production and is not due to non-specific cytotoxicity by CSE. Captopril attenuates CSE-induced endothelial dysfunction partly through scavenging free radicals.
Ota
Y
Y
Division of Cardiology, Kumamoto University School of Medicine, Honjo, Kumamoto City, Japan.
Kugiyama
K
K
Sugiyama
S
S
Ohgushi
M
M
Matsumura
T
T
Doi
H
H
Ogata
N
N
Oka
H
H
Yasue
H
H
D000111:Acetylcysteine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology*; D002455:Cell Division; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D010947:Plants, Toxic; D011817:Rabbits; D012907:Smoking / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014026:Nicotiana; D014471:Umbilical Veins; D014664:Vasodilation
D000806:Angiotensin-Converting Enzyme Inhibitors; D016166:Free Radical Scavengers; D005609:Free Radicals; D009569:Nitric Oxide; D002216:Captopril; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine