SMOKING IMPAIRS THE ACTIVITY OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE IN SAPHENOUS-VEIN

Smoking impairs the endothelium-dependent relaxation of arteries and v eins, with the maximum relaxation in response to the calcium ionophore A23187 of saphenous vein rings being reduced from 53 +/- 4% in nonsmo kers to 27 +/- 5% in smokers. We have investigated whether this endoth elial dysfunction was attributable to altered activity or concentratio n of nitric oxide synthase (NOS). The concentration of NOS in saphenou s vein endothelium, determined by Western blotting and immunohistochem istry, was not different in nonsmokers and smokers. Nitrite production from vein strips stimulated with A23187 was higher in nonsmokers (med ian 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 N-G-monomethyl-L-arginine. Organ cham ber studies to monitor the endothelium-dependent relaxation of vein ri ngs in response to A23187 showed that preincubation of rings from smok ers with either L-arginine (3 mmol/L) or superoxide dismutase (250 U/m L) did not improve the maximum relaxation. In contrast, preincubation of vein rings from smokers with 20 mu mol/L tetrahydrobiopterin increa sed the maximum relaxation from 27 +/- 5% to 51 +/- 6%, P=.01. Preincu bation of vein from smokers with tetrahydrobiopterin also significantl y increased nitrite and cGMP production in response to stimulation wit h A23187. The impaired endothelium-dependent relaxation of saphenous v ein rings from smokers appears to be caused by a reduction in the acti vity of endothelial NOS that is attributable to an inadequate supply o f the coenzyme tetrahydrobiopterin.