Heavy and light cigarette smokers have similar dysfunction of endothelial vasoregulatory activity: an in vivo and in vitro correlation.

ABSTRACT

OBJECTIVES: The goal of this study was to investigate the dose-dependent effects of active cigarette smoking on endothelial nitric oxide (NO) and endothelin-1 (ET-1) biosynthesis. BACKGROUND: Limited studies have suggested that active cigarette smoking may be associated with a dose-dependent reduction of endothelium-dependent vasodilation (EDV). The underlying biochemical changes that cause this dose-specific effect, such as changes in the endothelial NO biosynthetic pathway and ET-1 production, have not been examined. METHODS: Flow- and nitroglycerin-mediated reactivity of the brachial artery were measured in eight nonsmokers, seven light smokers (< or =1 pack/week) and eight heavy smokers (> or =1 pack/day), and their sera were added to confluent ( approximately 85%) monolayers of human umbilical endothelial cells (HUVECs) for 12 h. Basal and substance P-stimulated NO and basal ET-1 production were measured. The HUVECs used for measuring basal NO production were lysed, and both endothelial NO synthase (eNOS) protein expression and eNOS activity were determined. RESULTS: Serum cotinine level and pack-years of smoking were significantly lower in light smokers compared with heavy smokers (p < 0.006 and p < 0.004, respectively). There were no significant differences between heavy smokers and light smokers in EDV (p = 0.52), basal- (p = 0.70) and stimulated-NO production (p = 0.95), eNOS protein (p = 0.40) and eNOS activity (p = 0.63). Compared with nonsmokers, all the parameters were significantly altered in both of the smokers' groups. No differences were found in nitroglycerin-mediated vasodilation and in vitro ET-1 production among the three groups. CONCLUSIONS: These results indicate light smoking may have similar detrimental effects on EDV and NO biosynthetic pathway as does heavy smoking. These data may have important implications concerning the amount of active cigarette exposure that imparts cardiovascular risk.