期刊
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
卷 52, 期 -, 页码 54-61出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.etap.2017.03.012
关键词
Cardiac hypertrophy; Inflammation; Nitric oxide; Oral contraceptive; Profibrotic biomarker
资金
- Basic Science Research Program through National Research Foundation of Korea (NRF) [2013R1A1A2058145, 2013K2A4A1044932]
- Ministry of Education, Science and Technology
- Korean Health Technology R D Project
- Ministry of Health and Welfare, Republic of Korea [HI13C1527]
- Kyungpook National University Research Fund
- National Research Foundation of Korea [2013R1A1A2058145] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Combined oral contraceptive (COC) use or inhibition of nitric oxide (NO) synthesis has been shown to cause hypertension and insulin resistance. However, the concomitant effects of COC and NO deficiency on the heart and glucose regulation are not well known. We therefore hypothesized that COC treatment during NO deficiency would lead to the development of cardiac hypertrophy that is associated with aggravated glucose deregulation, pro-inflammatory and pro-fibrotic biomarkers. Eight-week-old female Wistar rats were randomly allotted into control, NO deficient (N-G-nitro-L-arginine methyl ester: L-NAME; 20.0 mg/kg b.w.), COC-treated (1.0 pg ethinylestradiol + 5.0 mu g levonorgestrel, p.o) and L-NAME + COC-treated groups. The animals were treated daily for 6 weeks. Systolic blood pressure was estimated by tail-cuff plethysmography, insulin resistance (IR) and f3-cell function were estimated by homeostatic model of assessment (HOMA-IR and HOMA-beta). Pro-inflammatory (C-reactive protein; CRP and uric acid) and pro-fibrotic (plasminogen activator inhibitor-1; PAI-1) biomarkers were estimated in the plasma. Cardiac histological examination was also done. Results show that COC or L NAME treatments led to increased blood pressure, HOMA-IR, impaired 5-cell function, PAI-1, CRP and uric acid, without significant effect on cardiac mass. L-NAME + COC-treated group had significantly higher blood pressure, HOMA-IR, impaired beta-cell function, PAI-1, CRP and cardiac mass than COC- or L-NAME-treated groups. Histological examination validated that COC use during NO deficiency causes cardiac hypertrophy. The present study demonstrates that COC treatment and NO deficiency synergistically causes cardiac hypertrophy that is associated with aggravated glucose deregulation, atherogenic dyslipidemia, pro-inflammatory and pro fibrotic markers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据