100. The effect of pitavastatin and pravastatin on omental and chorionic plate artery function in normal pregnancy and pre-eclampsia

Abstract

Introduction There are no effective therapies for pre-eclampsia (PE), which remains a leading cause of considerable materno-fetal morbidity and mortality. Statins, widely utilized in cardiovascular disease, represent a candidate therapy for PE. Determination of statins’ ability to ameliorate the observed endothelial dysfunction in PE is lacking. Objective To determine the effect of short-term pitavastatin and pravastatin exposure on chorionic plate arteries (CPAs) and omental arteries (OAs) from normal and PE pregnancies. Methods CPAs and OAs from normal pregnancy (NP; N = 43 placentas, N = 20 biopsies) and PE (N = 18 placentas, N = 5 biopsies) pregnancies were mounted on a wire myograph. Contraction was assessed with KPSS (120 mM) and thromboxane-mimetic U46619 (0.1 nM–2 μM). Arteries were incubated for 2 h with 1 μM pitavastatin or pravastatin; time-controls in parallel. U46619 dose–response curves were repeated or NO-donor SNP (1 nM–100 μM) or endothelium-dependent bradykinin (0.1–1000 nM/L) following U46619 pre-constriction. All data are mean ± SEM. Results Neither statin significantly altered vascular reactivity in NP CPAs. CPAs show blunted SNP-induced relaxation in PE vs. NP (38 ± 10% vs. 28 ± 12% respectively; p = 0.038; Two-way ANOVA). Additionally, 1μM pitavastatin attenuated PE CPAs vasoconstriction compared to control (Emax, 152 ± 30% and 165 ± 33% respectively; p = 0.013; Two-way ANOVA) but vasodilation was unaffected. In NP OAs, 1μM pravastatin reduced vasoconstriction compared to time-control (111 ± 20% and 123 ± 23% respectively; p = 0.044; Two-way ANOVA) but did not affect vasodilation. Preliminary PE OA data suggests neither statin had a significant effect on vasoconstriction or vasodilatation (P > 0.05; Two-way ANOVA; N = 5). Discussion Data suggests statins are unlikely to be deleterious to placental vascular function in NP. Pitavastatin (PE CPAs) and pravastatin (NP OAs) have the ability to blunt agonist-induced vasoconstriction. Future work will focus on whether pitavastatin and pravastatin improve endothelial function in OAs from women with PE.