Smoking has been shown to decrease subcutaneous tissue oxygen (PsqO2). This is thought to be due to the sympathomimetic effects of nicotine. Clonidine is a centrally acting alpha 2 adrenergic agonist which decreases sympathetic output. This study is thus being performed to see if clonidine, by blocking the sympathetic output caused by smoking, can prevent or decrease the drop in PsqO2. To achieve this, healthy volunteers will be asked to smoke and the decrease in PsqO2 measured. An interval of approximately 1 hour will be allowed for the. effects of nicotine to wear off. Clonidine or a placebo drug will be subsequently administered. Two hours later at peak plasma concentration for clonidine, the subjects will be asked to smoke again and subcutaneous oxygen tension will be monitored. This study will be repeated a week later on the same subject, who will receive the other drug that they did not receive in the first round. Both drugs will be administered in a randomized order. The use of placebo allows the effect of consecutive smoking sessions on Psq02 to be monitored. We intend to carry out all study procedures and measurements in the GCRC. Subjects will be admitted in the morning on both days of the study and discharged late afternoon. The study will take 8 hours on each day.
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