Abstract 030: Low-dose Aspirin During Pregnancy Does Not Prevent Augmentation of Arterial Contractions to Thromboxane A 2 in a Rat Model of Pregnancy-Induced Hypertension

Abstract

Background: Daily intake of low dose aspirin after 12 weeks of gestation is currently recommended as a preventative intervention in pregnancies at high risk of developing preeclampsia. We previously showed that treating pregnant rats with a synthetic ligand of Toll-like receptor 9 (TLR9; ODN2395) activated the innate immune system causing preeclampsia-like characteristics such as maternal hypertension, vascular oxidative stress, and augmented vascular responses to thromboxane A 2 (TxA 2 ). Hypothesis: Low-dose aspirin treatment would ameliorate ODN2395-induced augmented responses to TxA 2 in maternal arteries. Methods: Pregnant rats were treated with ODN2395 (300 μg) or vehicle on gestational day (GD) 14, 16, 18. Daily low-dose aspirin treatment (1.5 mg/kgBW) started on GD10 and continued throughout gestation. Systolic blood pressure was measured using the tail-cuff method on GD19. On GD21, uterine (UTA) and mesenteric resistance artery (MES) responses to a TxA 2 mimetic (U46619, 10 -9 -10 -6 M) was measured with a wire myograph. Results: Uterine arteries from the ODN2395+Aspirin-treated group had greater contractile responses to U46619 compared to all other groups [Emax, %KCl: Control (n=6): 109.2±8.8; ODN2395 (n=5): 124.4±20.2; Aspirin (n=5): 76.08±11.2; ODN2395+Aspirin (n=5): 134.7±4.5, p<0.05]. Aspirin alone reduced MES responses to U46619 compared to control and MES from ODN2395 and ODN2395+Aspirin groups had greater contractile responses to U46619 compared to Aspirin alone [Emax, %KCl: Control (n=8): 109.8±5.2; ODN2395 (n=6): 111.1±4.3; Aspirin (n=7): 89.4±3.6; ODN2395+Aspirin (n=8): 121.7±6.3, p<0.05]. Rats treated with ODN2395 and ODN+Aspirin had greater systolic blood pressure compared to control rats [control (n=8): 97.3±3.2 mmHg, ODN2395 (n=6): 121.3±4.3 mmHg, Aspirin (n=8): 100.3±2.9 mmHg, ODN2395+Aspirin (n=7): 127.5 ±6.7 mmHg, p<0.05]. Conclusion: Exposure to a TLR9 agonist during pregnancy resulted in augmented contractile responses to a TxA 2 mimetic in maternal arteries when rats were in a regime of low-dose aspirin. This was shown in arteries from both reproductive and non-reproductive vascular beds.