title: Effect of nicotine on the intimal hyperplasia after endothelial removal of the rabbit carotid artery.
abstract: 1. The present experiments were designed to investigate the effect of long-term oral nicotine (10 mg/200 ml/kg/day for 7 weeks) on the intimal hyperplasia after endothelial removal of the rabbit carotid artery. 2. The plasma concentrations of nicotine were determined to be 11.7-12.5 ng/ml during the term of administration and corresponded to the plasma levels in human smokers. 3. Six weeks after the endothelial removal, light microscopy revealed a marked intimal hyperplasia. Administration of nicotine tended to accelerate the intimal hyperplasia, which was estimated by comparing the histological findings, DNA content and wet weight of the vessel wall. 4. Acetylcholine- and A23187-induced endothelium-dependent relaxations were greatly impaired in the hyperplastic artery strips. The impairment of relaxations tended to be accelerated in the nicotine group. Sodium nitroprusside-induced relaxation was not different between the control and the hyperplastic artery strips and remained unaffected in the nicotine group. 5. The concentrations of endogenous nitric oxide (NO) synthesis inhibitors, NG-monomethyl-L-arginine (L-NMMA) and asymmetrical NG,NG-dimethyl-L-arginine (ADMA) were significantly more increased in the regenerated endothelial cells compared with those in the control endothelial cells. The concentrations of L-NMMA and ADMA in the regenerated endothelial cells were significantly increased by as much as 1.3 x 10(-6) and 5.6 x 10(-7) M, respectively, in the nicotine group. 6. Immunoreactive endothelin-1 was significantly increased in the hyperplastic vessel wall (2.4 times that of the control) in 6 weeks. Administration of nicotine tended to increase the level. 7. It seems possible to assume from these results that, although, under the present experimental conditions, nicotine exhibited a tendency to accelerate the intimal hyperplasia after endothelial removal, the longer exposure to nicotine or a higher dose of the agent or both would significantly accelerate the intimal hyperplasia through the enhanced impairment of endothelium-derived relaxing factor/ NO production, which might be brought about by the enhanced increases in L-NMMA and ADMA concentrations, and the enhanced increase in endothelin-1 in the vessel wall.
authors.affiliation: Department of Medicinal Chemistry, Institute for Medical and Dental Engineering, Tokyo Medical and Dental University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hamasaki
authors.forename: J
authors.initials: J
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Masuda
authors.forename: S
authors.initials: S
authors.lastname: Tamaoki
authors.forename: E
authors.initials: E
authors.lastname: Isotani
authors.forename: S
authors.initials: S
authors.lastname: Obayashi
authors.forename: T
authors.initials: T
authors.lastname: Udagawa
authors.forename: H
authors.initials: H
authors.lastname: Azuma
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006965:Hyperplasia; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D019323:omega-N-Methylarginine / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D019323:omega-N-Methylarginine; C018524:N,N-dimethylarginine; D009538:Nicotine; D001120:Arginine; D019001:Nitric Oxide Synthase