CHRONIC NICOTINE ADMINISTRATION DOES NOT AFFECT PERIPHERAL VASCULAR REACTIVITY IN THE RAT

The effect of chronic nicotine exposure on vascular function and neuro transmitter content was studied in the Fisher 344 rat. Implantation of osmotic mini pumps containing nicotine (0.18-4.7 mg/kg/day) for 14 da ys resulted in dose-related levels of plasma nicotine (up to 362+/-15 ng/ml) and its major metabolite cotinine (1545+/-40 ng/ml), as measure d by gas chromatography. Rat body weight increase was inhibited signif icantly by 4.7 mg/kg/day of nicotine exposure. In the isolated perfuse d mesentery, transmural nerve stimulation of capsaicin-sensitive senso ry nerves produced vasodilator responses that were not different betwe en vehicle- and chronic nicotine-treated animals. Endothelium-dependen t vasodilation elicited by acetylcholine also was not influenced by ch ronic nicotine treatment. Furthermore, chronic nicotine exposure in vi vo had no effect on in vitro vasodilator responses caused by nicotine itself, either at low (3 x 10(-5) M) or high (3 x 10(-4) M) concentrat ions. In tail artery ring segments, vasoconstrictor responses to eithe r transmural adrenergic nerve stimulation or norepinephrine were not d ifferent when vehicle and nicotine treatment groups were compared. Pri or chronic nicotine exposure also did not alter nicotine's ability to relax ring segments that were precontracted with norepinephrine. Vascu lar contents of norepinephrine, calcitonin gene-related peptide, neuro peptide Y and substance P were not altered by chronic nicotine treatme nt. In conclusion, although nicotine has direct vascular actions, chro nic nicotine exposure up to 4.7 mg/kg/day does not significantly alter vascular reactivity.