Nicotine Patch, Blood Flow and Oxidative Stress Study

The Effect Of Nicotine On Indices Of Arterial Function And Oxidative Stress

This study will address the hypothesis that nicotine, like cigarette smoking acting as a pro-oxidant may have adverse effects on arterial function.

Smoking causes >400,000 deaths from cardiovascular disease (CVD) per year. The molecular basis of smoking induced tissue injury remains unclear but considerable evidence supports a role for oxidant stress (OS).

Arterial function has been shown to be impaired in smokers even before the onset of angiographically demonstrable atherosclerosis. Defects in endothelium dependant flow mediated vasodilatation (FMD) are seen in those at risk of or with overt vascular disease.

Cigarette smoking is highly addictive. Spontaneous quit rates approximate 3%. Even those using nicotine replacement therapy (NRT) have high relapse rates (67-75%) on completion of the 8-12 week course of NRT. Thus there is interest in the use of extended NRT as a "safer" alternative to cigarette smoking. However such assumptions may be premature. Nicotine demonstrates proxidant effects in vitro and in small studies has been associated with endothelial dysfunction. Studies simultaneously assessing the effects of nicotine on oxidative stress and arterial function in humans have not been performed.

The current proposal will address the hypothesis that nicotine, like cigarette smoking acting as a pro-oxidant may have adverse effects on arterial function.

Inclusion Criteria:

• Healthy individuals
• Nonsmokers who have never smoked
• Normal medical history
• Normal physical examination
• Normal laboratory data
• Negative urinary pregnancy test for females

Exclusion Criteria:

• Previous CVD
• Chronic medication use
• History alcoholism
• History of smoking
• Current pregnancy
• Subjects, who have less than or equal to 60% platelet aggregation in response to arachidonic acid will also be excluded.