Olatunji Lawrence Aderemi, Michael Olugbenga Samuel, Adeyanju Oluwaseun Aremu, Areola Emmanuel Damilare, Soladoye Ayodele Olufemi
Cardiovascular Research Laboratory, Department of Physiology, College of Health Sciences University of Ilorin, Ilorin, Nigeria.
Cardiovascular Research Laboratory, Department of Physiology, College of Health Sciences University of Ilorin, Ilorin, Nigeria.
Pharmacol Rep. 2017 Jun;69(3):512-519. doi: 10.1016/j.pharep.2016.12.010. Epub 2016 Dec 19.
Reports showed that estrogen-progestin oral contraceptive (COC) or tobacco smoking causes increased risk of cardiovascular diseases (CVD) in premenopausal women. Studies also suggest that nicotine, a major tobacco alkaloid, may worsen or improve atherothrombotic CVD. Altered hemorheology, prothrombotic and pro-inflammatory biomarkers, have been implicated in the development of atherothrombotic CVD events. However, the effect of non-smoking nicotine exposure on these biomarkers during COC treatment is not yet established. We therefore sought to determine the effects of nicotine exposure during COC treatment on these biomarkers, and also tested the hypothesis that the nicotine effects would be glucocorticoid-dependent.
Female Sprague-Dawley rats aged 10 weeks were given (po) vehicle, low-dose nicotine (0.1mg/kg) or high-dose nicotine (1.0mg/kg) with or without COC steroids (5.0μg/kg ethinylestradiol and 25.0μg/kg levonorgestrel) daily for 6 weeks.
COC treatment or nicotine exposure led to increased insulin resistance (IR), hemorheological (blood viscosity, hematocrit and plasma viscosity), prothrombotic (plasminogen activator inhibitor-1), pro-inflammatory (uric acid, C-reactive protein, neutrophil/lymphocyte and platelet/lymphocyte ratios) biomarkers and corticosterone. However, these effects except that on corticosterone were abrogated by nicotine exposure during COC treatment.
Our study indicates that nicotine- or COC-induced IR may be mediated via inflammatory/thrombotic pathway. The results imply that nicotine exposure could impact negatively on atherothrombotic biomarkers in COC non-users, whereas the impact in COC users could be positive. The results also suggest that the anti-inflammatory, antithrombotic and blood viscosity-lowering effects of nicotine exposure during COC use is circulating glucocorticoid-independent.
报告显示，雌激素 - 孕激素口服避孕药（COC）或吸烟会增加绝经前女性患心血管疾病（CVD）的风险。研究还表明，主要烟草生物碱尼古丁可能会使动脉粥样硬化血栓形成性CVD恶化或改善。血液流变学改变、促血栓形成和促炎生物标志物与动脉粥样硬化血栓形成性CVD事件的发生有关。然而，在COC治疗期间非吸烟性尼古丁暴露对这些生物标志物的影响尚未确定。因此，我们试图确定COC治疗期间尼古丁暴露对这些生物标志物的影响，并检验尼古丁效应是否依赖糖皮质激素的假设。
10周龄雌性Sprague-Dawley大鼠每天经口给予溶剂、低剂量尼古丁（0.1mg/kg）或高剂量尼古丁（1.0mg/kg），同时给予或不给予COC类固醇（5.0μg/kg炔雌醇和25.0μg/kg左炔诺孕酮），持续6周。
COC治疗或尼古丁暴露导致胰岛素抵抗（IR）增加、血液流变学指标（血液粘度、血细胞比容和血浆粘度）、促血栓形成指标（纤溶酶原激活物抑制剂-1）、促炎指标（尿酸、C反应蛋白、中性粒细胞/淋巴细胞和血小板/淋巴细胞比率）以及皮质酮升高。然而，除了对皮质酮的影响外，COC治疗期间的尼古丁暴露消除了这些影响。
我们的研究表明，尼古丁或COC诱导的IR可能通过炎症/血栓形成途径介导。结果表明，尼古丁暴露可能对未使用COC的人群的动脉粥样硬化血栓形成生物标志物产生负面影响，而对使用COC的人群可能产生正面影响。结果还表明，COC使用期间尼古丁暴露的抗炎、抗血栓和降低血液粘度的作用与循环糖皮质激素无关。
