NICOTINE AVERTS CARDIORENAL DYSFUNCTION BY MITIGATING ESTROGEN-PROGESTIN-INDUCED IMPAIRED NA+/K+-ATPASE ACTIVITY AND TRIGLYCERIDE ACCUMULATION IN INSULIN RESISTANT FEMALE RATS

Abstract

Objective: Roughly fifty percent of premenopausal women who smoke cigarettes are also on hormonal contraceptives, especially oral estrogen-progestin therapy. Oral estrogen-progestin therapy has been reported to promote insulin resistance (IR), a major risk factor for the development of cardiometabolic dysfunction. Impaired Na+/K+ -ATPase activity has also been associated with cardiometabolic disturbances. The effects of nicotine on cardiorenal metabolic dysfunctions during estrogen-progestin therapy have not been fully elucidated. It is therefore hypothesized that nicotine would ameliorate IR that is accompanied by improved cardiorenal Na+/K+-ATPase activity, uric acid, oxidative stress and lipid accumulation in estrogen-progestin-treated rats. Design and method: Female Wistar rats (n = 6/group) aged 10 weeks were given (po) vehicle, nicotine (1.0 mg/kg) with or without estrogen-progestin steroids (1.0 μg ethinylestradiol and 5.0 μg levonorgestrel) daily for 6 weeks. The insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA-IR). Results: Data showed that estrogen-progestin treatment or nicotine exposure led to insulin resistance, hyperinsulinemia, increased cardiac and renal uric acid, malondialdehyde, triglyceride, glycogen synthase kinase-3, plasminogen activator inhibitor-1, alkaline phosphatase, aspartate transaminase, alanine transferase activity and reduced bilirubin. Estrogen-progestin treatment led to decreased cardiac Na+/K+-ATPase activity while nicotine did not alter the activity. Renal Na+/K+-ATPase activity was not altered by the treatment. However, these alterations were ameliorated by nicotine exposure plus estrogen-progestin treatment Conclusions: The results showed that oral nicotine enhanced cardiorenal Na+/K+-ATPase activity and suppressed lipid accumulation, oxidative stress, inflammation and thrombotic tendency in estrogen-progestin-induced insulin resistance. Therefore, the findings of the present study imply that oral nicotine may be cardiorenal protective especially during estrogen-progestin therapy.