title: Time and dose effect of transdermal nicotine on endothelial function.
abstract: Nicotine patches are available as an over-the-counter medication for aid in smoking cessation. This study was designed to determine how nicotine patch therapy over time and dose ranges used in smoking cessation programs in humans affects endothelium-dependent relaxations. Dogs were treated with nicotine patches (11, 22, or 44 mg/day) for 2 and 5 wk. Circulating nicotine and oxidized products of nitric oxide (NOx) were measured. Coronary arteries were prepared for measurement of isometric force and aortic endothelial cells were prepared for measurement of mRNA or NO synthase (NOS) activity. Circulating nicotine increased with increasing concentrations of nicotine patches. After 5 wk of treatment with 22 mg/day patches, circulating NOx was reduced but NOS activity was increased. NOS mRNA was similar among groups. Only after 5 wk of treatment with 22 mg/day patches were endothelium-dependent relaxations reduced to alpha(2)-adrenergic agonists, ADP, and the calcium ionophore A-23187. These results suggest a time and biphasic dose effect of nicotine treatment on endothelium-dependent responses that may be related to bioavailability of NO. This complex relationship of duration and dose of nicotine treatment may explain, in part, discrepancies in effects of nicotine on endothelium-dependent responses.
authors.affiliation: Departments of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. miller.virginia@mayo.edu
authors.forename: V M
authors.initials: VM
authors.lastname: Miller
authors.forename: W D
authors.initials: WD
authors.lastname: Clouse
authors.forename: B H
authors.initials: BH
authors.lastname: Tonnessen
authors.forename: U S
authors.initials: US
authors.lastname: Boston
authors.forename: S R
authors.initials: SR
authors.lastname: Severson
authors.forename: S
authors.initials: S
authors.lastname: Bonde
authors.forename: K S
authors.initials: KS
authors.lastname: Rud
authors.forename: R D
authors.initials: RD
authors.lastname: Hurt
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000279:Administration, Cutaneous; D000818:Animals; D001011:Aorta / Q000201:enzymology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D003367:Cotinine / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007476:Ionophores; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D019323:omega-N-Methylarginine; D000001:Calcimycin; D000244:Adenosine Diphosphate; D009538:Nicotine; D019001:Nitric Oxide Synthase; D003367:Cotinine; D002118:Calcium