Uterine blood flow and catecholamine response to repetitive nicotine exposure in the pregnant ewe

In order to simulate human smoking, experiments were designed to determine what dose of nicotine in the pregnant sheep would produce those plasma nicotine concentrations observed in human smokers and to measure uterine blood flow and plasma catecholamines in response to repetitive exposure (every 30 minutes) to that nicotine dose. Utilizing seven chronically catheterized pregnant sheep equipped with electromagnetic flow probes around both uterine arteries, we observed that a nicotine dose of 0.2 mg/min for 5 minutes results in mean plasma nicotine concentrations of 23.1 +/- 1.1 ng/ml SEM (n = 17) immediately following infusion. This dose of nicotine was then infused every 30 minutes for 4 hours, and aliquots of blood were drawn immediately before and after nicotine infusion for determination of plasma catecholamines. No significant alterations in plasma epinephrine and norepinephrine were observed throughout the experiments (n = 8), and no significant changes in uterine blood flow occurred at any time during the experiment (n = 30). We conclude that there is a species difference between sheep and man with respect to the nicotinic threshold for catecholamine release.