Chronic nicotine administration does not affect peripheral vascular reactivity in the rat.
The effect of chronic nicotine exposure on vascular function and neurotransmitter content was studied in the Fisher 344 rat. Implantation of osmotic mini pumps containing nicotine (0.18-4.7 mg/kg/day) for 14 days resulted in dose-related levels of plasma nicotine (up to 362 +/- 15 ng/ml) and its major metabolite cotinine (1545 +/- 40 ng/ml), as measured by gas chromatography. Rat body weight increase was inhibited significantly by 4.7 mg/kg/day of nicotine exposure. In the isolated perfused mesentery, transmural nerve stimulation of capsaicin-sensitive sensory nerves produced vasodilator responses that were not different between vehicle- and chronic nicotine-treated animals. Endothelium-dependent vasodilation elicited by acetyl-choline also was not influenced by chronic nicotine treatment. Furthermore, chronic nicotine exposure in vivo 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) concentrations. In tail artery ring segments, vasoconstrictor responses to either transmural adrenergic nerve stimulation or norepinephrine were not different when vehicle and nicotine treatment groups were compared. Prior chronic nicotine exposure also did not alter nicotine's ability to relax ring segments that were precontracted with norepinephrine. Vascular contents of norepinephrine, calcitonin gene-related peptide, neuropeptide Y and substance P were not altered by chronic nicotine treatment. In conclusion, although nicotine has direct vascular actions, chronic nicotine exposure up to 4.7 mg/kg/day does not significantly alter vascular reactivity.
Li
Z
Z
Department of Pharmacology, College of Medicine, University of California, Irvine.
Barrios
V
V
Buchholz
J N
JN
Glenn
T C
TC
Duckles
S P
SP
D000818:Animals; D001808:Blood Vessels / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D003367:Cotinine / Q000097:blood; D004361:Drug Tolerance; D004730:Endothelium, Vascular / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009479:Neuropeptides / Q000032:analysis; D018377:Neurotransmitter Agents / Q000032:analysis; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D009479:Neuropeptides; D018377:Neurotransmitter Agents; D009538:Nicotine; D003367:Cotinine