[PS 01-02] Combined oral contraceptive and nitric oxide synthesis inhibition synergistically causes cardiac hypertrophy and fibrosis in hypertensive insulin-resistant female rats

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Combined oral contraceptive (COC) use or inhibition of nitric oxide (NO) synthesis has been shown to cause hypertension and insulin resistance. However, the concomitant effect of COC and NO deficiency on the heart is not well known. We therefore hypothesize that NO deficiency during COC treatment would lead to cardiac hypertrophy and fibrosis.

Design and method:

Eight-week-old female Wistar rats were randomly allotted into control, NO deficient (NG-nitro-L-arginine methyl ester: L-NAME; 20.0 mg/kg b.w.), COC-treated (1.0 μg ethinylestradiol + 5.0 μg levonorgestrel, p.o) and L-NAME+COC-treated groups. The animals were treated daily for 8 weeks. Blood pressure was estimated by tail-cuff plethysmography while insulin resistance (IR) was estimated by homeostatic model of assessment (HOMA-IR). Profibrotic (plasminogen activator inhibitor-1; PAI-1) and proinflammatory (C-reactive protein; CRP and uric acid) markers 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, PAI-1, CRP and uric acid, without significant effect on heart weight. L-NAME+COC-treated group had significantly higher blood pressure, HOMA-IR, PAI-1, CRP and heart weight than COC- or L-NAME-treated groups. Histological examination validated that NO deficiency during COC use causes cardiac hypertrophy and fibrosis.


The present study demonstrates that COC treatment and NO deficiency synergistically causes cardiac hypertrophy which is associated with increased fibrosis and inflammation.

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