(411) Effect of aspirin on mechanical properties of mesenteric arteries in a mouse model of preeclampsia

Prior ex vivo animal studies have shown that acetylsalicylic acid (ASA) causes direct vasodilation of resistance vessels. The objective of this study is to understand the effect of ASA on the mechanical properties of mesenteric arteries in a murine model of preeclampsia (PE) and to further characterize ASA’s mechanism of PE risk reduction.

Study Design:

Mesenteric arteries from a mouse model of PE and healthy gravid mice at 17.5 days gestation were dissected into rings and mounted to a Multi-Wire Myograph System. Arterial rings were precontracted with norepinephrine. Cumulative dose-response curves were calculated for ASA (0.001-0.006 µM), Calcitonin Gene-Related Peptide/CGRP (10^-10 – 10^-7 M), a known endothelium-independent vasodilator, and acetylcholine (10^-10 – 10^-5 M), a known endothelium-dependent vasodilator. The relaxation response was calculated as percent inhibition of the initially induced contraction, and the maximum possible effect for the reagent (E_max) was calculated accordingly. The concentration of each reagent required to reduce tension by 50% (ED₅₀) was calculated when able.  Student’s t-test was used for statistical analysis.

Results:

Sixteen arterial rings from the PE model (n=4 mice) and 14 from healthy gravid mice (n=4) were included after excluding non-functioning channels and rings that did not demonstrate sustained contraction. E_max values (mean ± standard error of the mean) in PE and healthy mice respectively were 34.70±3.97 and 71.63±5.25% for ASA, 90.09±1.67 and 94.53±1.43% for CGRP, and 86.43±2.5 and 95.08±1.57% for acetylcholine. Mean E_max was significantly different between the PE and healthy groups for all reagents. ED₅₀ could not be calculated for ASA. ED₅₀ was significantly different between the PE and healthy groups for acetylcholine but not for CGRP, demonstrating altered endothelium in PE.

Conclusion:

ASA does not have a direct vasodilatory effect on mesenteric arteries in a mouse model of PE. Thus, the ability of ASA to reduce preeclampsia risk may be due to its effects in early pregnancy at sites outside of the vasculature which alter the endothelium.