CLINICAL STUDY
Heavy and light cigarette smokers have similar dysfunction of endothelial vasoregulatory activity
An in vivo and in vitro correlation
Rajat S. Barua, MD* ,
John A. Ambrose, MD, FACC*,*,
Lesley-Jane Eales-Reynolds, PhD ,
Mary C. DeVoe, RN*,
John G. Zervas, RCDS* and
Dhanonjoy C. Saha, PhD*
* Saint Vincent Catholic Medical Centers, New York, New York, USA
the School of Biomedical and Life Sciences, University of Surrey, Guildford, UK
* Reprint request and correspondence: Dr. John A. Ambrose, The Comprehensive Cardiovascular Center, Department of Medicine, Saint Vincent Catholic Medical Centers of New York, 170 West 12th Street, New York, New York 10011, USA. jambrose{at}saintvincentsnyc.org
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 ( 1 pack/week) and eight heavy smokers ( 1 pack/day), and their sera were added to confluent ( 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.
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Abbreviations and Acronyms
| | ANOVA | | analysis of variance | | EC | | endothelial cells | | EDV | | endothelium-dependent vasodilation | | EGM | | endothelial growth media | | eNOS | | endothelial nitric oxide synthase | | ET-1 | | endothelin-1 | | HUVEC | | human umbilical endothelial cells | | mRNA | | messenger ribonucleic acid | | NO | | nitric oxide | | PLSD | | protected least significant difference | | SP | | substance P |
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