Long-term nicotine treatment reduces cerebral cortical vasodilation mediated by alpha4beta2-like nicotinic acetylcholine receptors in rats.
Regional cortical cerebral blood flow is increased via activation of brain nicotinic acetylcholine receptors. Acute intravenous injection of nicotine increases cortical blood flow, without changing systemic blood pressure in anesthetized rats. Here, we examined whether the nicotine-induced cerebral cortical vasodilation is affected by chronic nicotine treatment. Rats received chronic subcutaneous nicotine (at a low or a high-dose) short-term (1 h) or long-term (14 days). Under urethane anesthesia, blood flow in the frontal cortex, before and after bolus injection of nicotine (0.3-30 microg/kg, i.v.) was measured by laser Doppler flowmetry. The threshold dose of nicotine (3 microg/kg, i.v.) producing vasodilation was not affected by chronic nicotine treatment. However, the vasodilation induced by nicotine at 30 microg/kg was reduced after long-term nicotine treatment (but not after short-term exposure). The degree of reduction was marked and was statistically significant with high-dose (100 microg/kg/h) nicotine; low-dose (33 microg/kg/h) nicotine had a small effect that was not statistically significant. In contrast, the vasodilation in the cortical vessels obtained by hypercapnia (inhalation of 10% CO2) was not changed by chronic nicotine treatment. The nicotine-induced cortical vasodilation was not influenced by methyllycaconitine, an alpha7-selective nicotinic antagonist, while it was completely abolished by dihydro-beta-erythroidine, an alpha4beta2-preferring nicotinic antagonist. We conclude that long-term nicotine treatment reduces the functional activity of alpha4beta2-like nicotinic receptors that mediate cortical vasodilation.
Uchida
Sae
S
Department of the Autonomic Nervous System, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan. suchida@tmig.or.jp
Hotta
Harumi
H
Kawashima
Koichiro
K
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D000157:Aconitine