Nicotine and vascular endothelial dysfunction in female ovariectomized rats: role of estrogen replacement therapy

• Published in: Journal of pharmacy and pharmacology 2012-01, Vol.64 (1), p.108-119
• Main Authors: El-Seweidy, Mohamed M., Mohamed, Hoda E., Asker, Mervat E., Atteia, Hebatallah H.
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Thoracic - metabolism; atherogenic index; Atherosclerosis - metabolism; Calcium - metabolism; Endothelin-1 - metabolism; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; eNOS; ERT; Estradiol - analogs & derivatives; Estradiol - therapeutic use; Estrogen Replacement Therapy; Female; Humans; Hydroxyproline - metabolism; Lipids - blood; Malondialdehyde - metabolism; Models, Animal; nicotine; Nicotine - toxicity; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - drug effects; Nitric Oxide Synthase Type III - genetics; Ovariectomy; Oxidative Stress - drug effects; Rats; Rats, Wistar; VED
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.2011.01377.x

Objectives  The protective effects of estrogen replacement therapy (ERT) against oxidative injury and endothelial dysfunction in the aortic tissues induced with nicotine in ovariectomized (OVX) rats were investigated. Methods  Female rats were divided into a sham‐operated group (n = 8) and four groups in which OVX rats received either vehicle (0.1 ml sesame oil, i.m., n = 8), or nicotine (0.1 mg/kg, s.c., n = 8), or estradiol benzoate (0.1 mg/kg, i.m., n = 8), or both nicotine and estradiol benzoate (n = 8) starting at week 5 after the surgery and continuing for the following 6 weeks. Key findings  ERT was effective in preventing the rise in plasma lipid profile, atherogenic index and the level of induced endothelin‐1 (ET‐1) in nicotine‐treated OVX rats. It also reduced aortic malondialdehyde, hydroxyproline levels, calcium content and caspase‐3 expression induced in nicotine‐treated OVX rats. ERT increased serum estradiol, high‐density lipoprotein cholesterol and nitric oxide levels in nicotine‐treated OVX rats. Furthermore, ERT was effective in restoring reduced glutathione and cyclic guanosine monophosphate contents and endothelial nitric oxide synthase expression in aortic tissues of nicotine‐treated OVX rats. Conclusions  Short‐term ERT could be a promising therapeutic strategy to minimize nicotine‐induced oxidative stress and vascular endothelial dysfunction in menopausal women subjected to environmental smoke.