Research Study on the Effects of Smoking on Arteries

• To assess the dose-related effects of cigarette smoking on COX activation. [ Time Frame: Twice during study day ] [ Designated as safety issue: No ]
• To assess the dose-related effects of cigarette smoking on novel indices of lipid peroxidation, protein oxidation and DNA modification by lipid adducts. [ Time Frame: Study day ] [ Designated as safety issue: No ]

The current proposal, will elucidate the role of oxidant stress (OS) on arterial function as measured by flow mediated vasodilation. In addition, the investigators will address the hypothesis, that a pro-oxidant might have different degrees of effects on different biological targets, by performing quantitative assessment of the effects of OS on lipids, proteins and DNA.

Chronic smokers (of between 4 and 20 years duration) and non-smokers will be recruited. Smokers will be allocated to a "light" group, smoking 4-10 cigarettes per day and a "heavy" smoking group who smoke 11-20 cigarettes per day. Non-smokers will be defined as those with a life time consumption of no more than 20 cigarettes, do not live or work in a smoky atmosphere. All individuals will have a normal history and clinical examination, including a normal EKG, urinalysis and serum chemistry, haemogram and negative urinary pregnancy test.

• Light smokers
  2 blood draws, 3 urine collections and a test called an FMD which tests the circulation in your arm via ultrasound will be performed on the study day. Subjects will bring their own cigarettes on that day and smoke their regular amount. Female subjects will also have a pregnancy test done on the test day.
• Heavy Smokers
  2 blood draws, 3 urine collections and a test called an FMD which tests the circulation in your arm via ultrasound will be performed on the study day. Subjects will bring their own cigarettes on that day and smoke their regular amount. Female subjects will also have a pregnancy test done on the test day.
• Non Smokers
  2 blood draws, 3 urine collections and a test called an FMD which tests the circulation in your arm via ultrasound will be performed on the study day. Female subjects will also have a pregnancy test done on the test day.

Inclusion Criteria:

• Chronic smokers (of between 4 and 20 years duration) and non-smokers will be recruited to the GCRC. Smokers will be allocated to a "light" group, smoking 4-10 cigarettes per day and a "heavy" smoking group who smoke 11-20 cigarettes per day.
• Non-smokers will be defined as those with a life time consumption of no more than 20 cigarettes, do not live or work in a smoky atmosphere.
• All individuals will have a normal history and clinical examination, including a normal EKG, urinalysis and serum chemistry, haemogram and negative urinary pregnancy test.

Exclusion Criteria:

• previously suffered an acute major cardiovascular event
• those with a chronic disease
• those taking chronic medication
• those with a history of alcoholism or substance abuse
• Ex-smokers
• Subjects, who have less than or equal to 60% platelet aggregation in response to arachidonic acid