Abstract
Acetylsalicylic acid (aspirin) exhibits a broad range of activities, including analgesic, antipyretic, and antiplatelet properties. Recent clinical studies also recommend aspirin prophylaxis in women with a high risk of pre-eclampsia, a major complication of pregnancy characterized by hypertension. We investigated the effect of aspirin on mesenteric resistance arteries and found outdiscovered the molecular mechanism underlying this action. Aspirin (10−12–10−6 M) was tested on pregnant rat mesenteric resistance arteries by a pressurized arteriography. Aspirin was investigated in the presence of several inhibitors of: (a) nitric oxide synthase (L-NAME 2 × 10−4 M); (b) cyclooxygenase (Indomethacin, 10−5 M); (c) Ca2+-activated K+ channels (Kca): small conductance (SKca, Apamin, 10−7 M), intermediate conductance (IKca, TRAM34, 10−5 M), and big conductance (BKca, paxilline, 10−5 M); and (d) endothelial-derived hyperpolarizing factor (high KCl, 80 mM). Aspirin caused a concentration-dependent vasodilation. Aspirin-vasodilation was abolished by removal of endothelium or by high KCl. Furthermore, preincubation with either apamin plus TRAM-34 or paxillin significantly attenuated aspirin vasodilation (p < 0.05). For the first time, we showed that aspirin induced endothelium-dependent vasodilation in mesenteric resistance arteries through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. By activating this molecular mechanism, aspirin may lower peripheral vascular resistance and be beneficial in pregnancies complicated by hypertension.
Highlights
Aspirin was tested on preconstricted MA and induced a dose-dependent vasodilation, aspirin, ethanol, induced much less vasodilation
Our results demonstrated that aspirin vasodilation of MA is endothelium-dependent, ofisabout
62% was achieved at 10−6 M, the relaxation effect was already obs mediated by the endothelial-derived hyperpolarizing factor (EDHF), and involves the calcium-activated potassium channels, SKca, at IKca, a very concentration of 10−11M, suggesting a high sensitivity of MA to aspirin andlow
Summary
The use of aspirin has been growing over the past decades. It was used as an analgesic, anti-inflammatory, and antipyretic drug, as well as an antiplatelet agent due to its ability to inhibit platelet aggregation [1,2]. Aspirin has been suggested for use in pregnancy with high cardiovascular risk to prevent the development of gestational hypertensive disorders, such as pre-eclampsia (PE) [3,4]. There is no cure for PE; the most effective management of the disease is delivery [6], which can worsen neonatal outcomes if it needs to be initiated early in pregnancy. Early-onset PE requires treatments that prevent preterm birth to enable optimal intrauterine fetal growth [6]
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