Aqueous smokeless tobacco extract impairs endothelium-dependent vasodilation in the oral mucosa.
The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff) modulates vasomotor tone in the oral mucosa in situ and, if so, to determine the mechanisms that mediated these responses. Using intravital microscopy, we found that the extract had no significant effects on diameter of resistance (second-order) arterioles [44 +/- 5 (SD) microns] in the hamster cheek pouch. However, it significantly attenuated vasodilation elicited by two endothelium-dependent agonists, acetylcholine and bradykinin (P < 0.05). These effects were specific because smokeless tobacco extract had no significant effects on vasodilation elicited by nitroglycerin, an endothelium-independent agonist. Indomethacin, a cyclooxygenase inhibitor, and SQ-29548, a thromboxane A2/prostaglandin H2-receptor antagonist, abrogated the attenuating effects of smokeless tobacco extract on acetylcholine- and bradykinin-induced vasodilation. These data indicate that an aqueous extract of smokeless tobacco impairs endothelium-dependent vasodilation in the oral mucosa in situ in a specific fashion and that these effects are mediated, in part, by cyclooxygenase products of arachidonic acid metabolism that stimulate thromboxane A2/prostaglandin H2 receptors.
Suzuki
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H
Department of Medicine, University of Illinois at Chicago 60612-7323, USA.
Gao
X P
XP
Olopade
C O
CO
Jaffe
H A
HA
Pakhlevaniants
S
S
Rubinstein
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I
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000098:blood supply* / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology; D010947:Plants, Toxic; D014030:Tobacco, Smokeless / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010936:Plant Extracts; D014665:Vasodilator Agents; C045749:SQ 29548; D007213:Indomethacin