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

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.