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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
DOUBLE
Enrollment
55
A 7mg transdermal nicotine patch will be applied to the subject's arm for an 8 hour period.
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Assess the dose-related effects of nicotine in humans, on novel indices of lipid peroxidation, protein oxidation and DNA modification by lipid adducts.
Time frame: 1 - 3 years
Assess the dose-related effects of nicotine in humans on COX activation.
Time frame: 1 year
Assess the dose-related effects of nicotine in humans on blood flow mediated arterial function.
Time frame: 3 - 6 months
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