EFFECTS OF LONG-TERM CIGARETTE-SMOKING ON ENDOTHELIUM-DEPENDENT RESPONSES IN HUMANS

Endothelial injury is a central feature of vascular disease induced by cigarette smoking and may act as a precursor for future atheroscleros is. Using forearm occlusion plethysmography, we studied the vascular r esponses to methacholine (an endothelium-dependent vasodilator) and so dium nitroprusside (an endothelium-independent vasodilator) infused ir ate the brachial artery of 35 long-term cigarette smokers and 16 nonsm oking subjects. N-G-monomethyl-L-arginine (L-NMMA), a stereospecific i nhibitor of nitric oxide production, was used to inhibit synthesis of nitric oxide in the endothelium. The reactive hyperemic response at pe ak and during recovery to the temporary interruption of forearm blood flow was also compared between groups. Smokers had elevated carboxyhem oglobin levels compared with nonsmokers (5.1 +/- 2.1% vs 0.8 +/- 0.4%; P <0.001). No differences were found in the peak or late hyperemic re sponses between groups. In smokers, the incremental infusions of metha choline and sodium nitroprusside increased forearm blood flow from 3.6 +/- 1.2 to 12.9 +/- 9.0 ml . min(-1). 100 ml(-1) and from 4.0 +/- 1.5 to 9.3 +/- 4.0 ml . min(-1). 100 ml(-1), respectively, compared with 3.2 +/- 1.0 to 13.5 +/- 5.6 ml . min(-1). 100 mL(-1) and from 2.9 +/- 0.7 to 8.6 +/- 4.2 ml . min(-1). 100 ml(-1) in nonsmoking subjects (p = NS). L-NMMA (4 mu mol/min for 5 minutes) significantly reduced forea rm blood flow in both smokers and nonsmokers from 4.1 +/- 1.4 to 3.4 /- 1.2 ml . min(-1). 100 ml(-1) and 3.8 +/- 0.7 to 2.3 +/- 0.5 mL . mi n(-1). 100 ml(-1), respectively (p <0.01 for both); and the decrement in forearm blood flow in nonsmokers was significantly greater than tha t recorded in smoking subjects (p <0.05), In this study, long-term cig arette smokers exhibited an impairment in basal, but not stimulated, n itric oxide-mediated vasodilation.