title: Fish oil blunted nicotine-induced vascular endothelial abnormalities possibly via activation of PPARγ-eNOS-NO signals.
abstract: Nicotine exposure is associated with an induction of vascular endothelial dysfunction (VED), a hallmark of various cardiovascular disorders. The present study investigated the effect of fish oil in nicotine-induced experimental VED. VED was assessed by employing isolated aortic ring preparation, estimating aortic and serum nitrite/nitrate, aortic superoxide anion generation, and serum TBARS, and carrying out electron microscopic and histological studies of thoracic aorta. Nicotine (2 mg/kg/day, i.p., 4 weeks) administration produced VED in rats by attenuating acetylcholine-induced endothelium-dependent relaxation in the isolated aortic ring preparation, decreasing aortic and serum nitrite/nitrate concentration, impairing endothelial integrity, and inducing vascular oxidative stress. Treatment with fish oil (2 mL/kg/day p.o., 4 weeks) markedly prevented nicotine-induced endothelial functional and structural abnormalities and oxidative stress. However, administration of GW9662, a selective inhibitor of PPARγ, to a significant degree attenuated fish oil-associated anti-oxidant action and vascular endothelial functional and structural improvements. Intriguingly, in vitro incubation of L-NAME (100 μM), an inhibitor of nitric oxide synthase (NOS), markedly attenuated fish oil-induced improvement in endothelium-dependent relaxation in the aorta of nicotine-administered rats. Nicotine administration altered the lipid profile by increasing serum total cholesterol, which was significantly prevented by fish oil treatment. The vascular protective potential of fish oil in preventing nicotine-induced VED may pertain to its additional properties (besides its lipid-lowering effect) such as activation of PPARγ and subsequent possible activation of endothelial NOS and generation of nitric oxide, and consequent reduction in oxidative stress.
authors.affiliation: Cardiovascular Pharmacology Division, Department of Pharmacology, Rajendra Institute of Technology and Sciences, Sirsa 125 055, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Taneja
authors.forename: Nanjaian
authors.initials: N
authors.lastname: Mahadevan
authors.forename: Pitchai
authors.initials: P
authors.lastname: Balakumar
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000648:ultrastructure; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D009538:Nicotine / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D005395:Fish Oils; D047495:PPAR gamma; D009569:Nitric Oxide; D009538:Nicotine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine