Impairment of nitric oxide synthase-dependent dilatation of cerebral arterioles during infusion of nicotine.
The effects of nicotine on nitric oxide synthase (NOS)-dependent reactivity of cerebral arterioles remain uncertain. Our first goal was to examine whether infusion of nicotine alters NOS-dependent reactivity of cerebral arterioles. Our second goal was to examine the mechanisms that may account for the effects of nicotine on cerebral arterioles. We measured the diameter of pial arterioles to NOS-dependent (ADP and acetylcholine) and NOS-independent (nitroglycerin) agonists before and after the infusion of nicotine (2 microg x kg(-1) x min(-1) iv for 30 min, followed by a maintenance dose of 0.35 microg x kg(-1) x min(-1)). ADP- and acetylcholine-induced vasodilatation was impaired after the infusion of nicotine. In contrast, nicotine did not alter vasodilatation to nitroglycerin. Next, we examined whether the impaired responses of pial arterioles during infusion of nicotine may be related to oxygen radicals. We found that application of superoxide dismutase or tetrahydrobiopterin during infusion of nicotine could prevent impaired NOS-dependent vasodilatation. Thus acute exposure of cerebral vessels to nicotine specifically impairs NOS-dependent dilatation via the production of oxygen radicals possibly related to an alteration in the utilization of tetrahydrobiopterin.
Fang
Qin
Q
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
Sun
Hong
H
Mayhan
William G
WG
D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D010841:Pia Mater / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
D018722:Nicotinic Agonists; D001708:Biopterins; D009538:Nicotine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; C003402:sapropterin