Effects of nicotine on production of endothelin and eicosanoid by bovine pulmonary artery endothelial cells.
To clarify the relationship between cigarette smoking and regulators of vascular tone derived from endothelium, the authors studied the acute and subacute effects of nicotine on endothelin and eicosanoid production by bovine pulmonary artery endothelial cells (BPAEC). The acute effects of nicotine were assessed by measuring the release of endothelin, prostaglandin I2 (PGI2), and thromboxane A2 (TXA2) from BPAEC after their incubation with a medium containing various concentrations of nicotine (10(-9) M - 10(-3) M) for 24 h. The subacute effects were assessed after 1 week's culture of BPAEC in the presence of nicotine (10(-7) M, 10(-3) M). Acute exposure to a high concentration of nicotine (10(-5) M - 10(-3) M) led to a significant inhibition of endothelin production by BPAEC. Nicotine, 10(-3) M, inhibited PGI2 production, but led to release of lactate dehydrogenase. Subacute exposure to nicotine (10(-3) M) also inhibited the production of endothelin and PGI2 by BPEAC. A high concentration of nicotine reduced the production of endothelin and PGI2 by BPAEC, probably due to the cytotoxicity of nicotine. Concentrations of nicotine comparable to the plasma levels of nicotine found in smokers (10(-9) - 10(-6) M) did not affect the release of endothelin and PGI2 from BPAEC. The mechanism of nicotine-induced vasoconstriction may be independent of the release of endothelin or PG derivatives from endothelial cells.
Department of Pulmonary Medicine, Jichi Medical School, Tochigi, Japan.
N
N
Suzuki
Y
Y
Ishii
S
S
Kitamura
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D015777:Eicosanoids / Q000096:biosynthesis*; D016232:Endothelins / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D013928:Thromboxane A2 / Q000096:biosynthesis
D015777:Eicosanoids; D016232:Endothelins; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D009538:Nicotine; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase