Smoking Impairs the Activity of Endothelial Nitric Oxide Synthase in Saphenous Vein

Abstract

Smoking impairs the endothelium-dependent relaxation of arteries and veins, with the maximum relaxation in response to the calcium ionophore A23187 of saphenous vein rings being reduced from 53 +/- 4% in nonsmokers to 27 +/- 5% in smokers. We have investigated whether this endothelial dysfunction was attributable to altered activity or concentration of nitric oxide synthase (NOS). The concentration of NOS in saphenous vein endothelium, determined by Western blotting and immunohistochemistry, was not different in nonsmokers and smokers. Nitrite production from vein strips stimulated with A23187 was higher in nonsmokers (median 23.6 nmol.cm-2.h-1) than smokers (median 3.3 nmol.cm-2.h-1), P=.001, this difference being abolished when vein strips were preincubated in the presence of NG-monomethyl-L-arginine. Organ chamber studies to monitor the endothelium-dependent relaxation of vein rings in response to A23187 showed that preincubation of rings from smokers with either L-arginine (3mmol/L) or superoxide dismutase (250 U/mL) did not improve the maximum relaxation. In contrast, preincubation of vein rings from smokers with 20 micromol/L tetrahydrobiopterin increased the maximum relaxation from 27 +/- 5% to 51 +/- 6%, P=.01. Preincubation of vein from smokers with tetrahydrobiopterin also significantly increased nitrite and cGMP production in response to stimulation with A23187. The impaired endothelium-dependent relaxation of saphenous vein rings from smokers appears to be caused by a reduction in the activity of endothelial NOS that is attributable to an inadequate supply of the coenzyme tetrahydrobiopterin.

Contribution of Endothelial Nitric Oxide to Blood Pressure in Humans

“…24 As expected, we found that the increase in blood pressure produced by L-NMMA in the presence of trimethaphan was significantly lower in smokers than in normal control subjects, reflecting an impaired contribution of eNO to their blood pressure. Despite the documented eNO deficiency in smokers, it is important to note that they had a normal blood pressure.…”

Not Acute but Chronic Hypertriglyceridemia Is Associated With Impaired Endothelium-Dependent Vasodilation

“…31 Whether deficiency of the cofactor tetrahydrobiopterin plays a role in HTG, as has been demonstrated in diabetes, smoking, and hypercholesterolemia, remains to be elucidated. [32][33][34] Finally, it is conceivable that high amounts of triglyceride-rich lipoproteins accumulate in endothelial cells, as was recently demonstrated in endothelial cells from atherosclerotic plaques in human coronary arteries. 35 Lipid accumulation is associated with structural changes in the cell that may impede its function.…”

Promoter polymorphism (−786t>C) in the endothelial nitric oxide synthase gene is associated with risk of sporadic breast cancer in non‐Hispanic white women age younger than 55 years

“…44 Consistent with these findings, we found that carriers of the À786C variant, particularly in smokers, ER-negative patients, or PR-negative patients, had a significantly increased risk of breast cancer. Exposure to cigarette smoke can suppress eNOS activity 45 and interfere with NO synthesis by choking off the supply of L-arginine. 46 Experiments have shown that treatment with cigarette smoke extracts reduces the efficiency of promoters containing the À786C allele but not those with the À786T allele.…”