Chronic exposure to nicotine alters endothelium-dependent arteriolar dilatation: effect of superoxide dismutase.
The first goal of this study was to determine whether chronic injection of nicotine alters endothelium-dependent arteriolar dilatation. We measured the diameter of cheek pouch resistance arterioles (approximately 50 microm in diameter) in response to endothelium-dependent (acetylcholine and ADP) and -independent (nitroglycerin) agonists in control hamsters and hamsters treated with nicotine (2 microg. kg-1. day-1 for 2-3 wk). In control hamsters, acetylcholine (0.1 and 1.0 microM) dilated arterioles by 13 +/- 2 and 31 +/- 3%, respectively, and ADP (1.0 and 10 microM) dilated arterioles by 18 +/- 1 and 30 +/- 1%, respectively. In contrast, acetylcholine (0.1 and 1.0 microM) dilated arterioles by only 5 +/- 2 and 12 +/- 3%, respectively, and ADP (1.0 and 10 microM) dilated arterioles by only 7 +/- 2 and 13 +/- 3%, respectively, in animals treated with nicotine (P < 0.05 vs. response in control hamsters). Nitroglycerin produced similar dose-related dilatation of cheek pouch arterioles in control and nicotine-treated hamsters. Our second goal was to examine a possible mechanism for impaired endothelium-dependent arteriolar dilatation during chronic treatment with nicotine. We found that superfusion of the cheek pouch microcirculation with superoxide dismutase (150 U/ml) restored impaired endothelium-dependent, but did not alter endothelium-independent, arteriolar dilatation in hamsters treated with nicotine. Superfusion with superoxide dismutase did not alter endothelium-dependent or -independent arteriolar dilatation in control hamsters. We suggest that chronic exposure to nicotine produces selective impairment of endothelium-dependent arteriolar dilatation via a mechanism related to 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. wgmayhan@mail.unmc.edu
Sharpe
G M
GM
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D002610:Cheek; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D000244:Adenosine Diphosphate; D009538:Nicotine; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D000109:Acetylcholine