Superoxide dismutase restores endothelium-dependent arteriolar dilatation during acute infusion of nicotine.
We previously showed [Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H2337-H2342, 1997] that nicotine impairs endothelium-dependent arteriolar dilatation. However, mechanisms that accounted for the effect of nicotine on endothelium-dependent vasodilatation were not examined. Thus the goal of this study was to examine the role of oxygen radicals in nicotine-induced impairment of arteriolar reactivity. We measured diameter of cheek pouch resistance arterioles (approximately 50 micrometer diameter) in response to endothelium-dependent (ACh and ADP) and -independent (nitroglycerin) agonists before and after infusion of vehicle or nicotine in the absence or presence of superoxide dismutase. ACh, ADP, and nitroglycerin produced dose-related dilatation of cheek pouch arterioles before infusion of vehicle or nicotine. Infusion of vehicle, in the absence or presence of superoxide dismutase (150 U/ml), did not alter endothelium-dependent or -independent arteriolar dilatation. In contrast, infusion of nicotine (2 microgram . kg-1 . min-1) impaired endothelium-dependent, but not -independent, arteriolar dilatation. In addition, the effect of nicotine on endothelium-dependent vasodilatation was reversed by topical application of superoxide dismutase. We suggest that nicotine impairs endothelium-dependent arteriolar dilatation via an increase in the synthesis/release of oxygen-derived free radicals.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, Nebraska 68198-4575, USA.
Sharpe
G M
GM
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D002610:Cheek; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009061:Mouth Mucosa / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000244:Adenosine Diphosphate; D009538:Nicotine; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D000109:Acetylcholine