Abstract
Background and aims: Magnesium sulfate (MgSO4) is widely used as tocolytic agent and for the prophylaxis of seizures in pre-eclampsia. Antenatal exposure to MgSO4 has been associated with a higher risk of patent DA in preterm infants. MgSO4 is a vasodilator and thus may exert a direct relaxant effect in the DA. Here we aimed to investigate the possible vasoactive effects of MgSO4 in the chicken DA.Design/Methods: Isolated rings of the DA from 15-d (E15) and 19-d (E19) chicken embryos (total incubation: 21-d) were mounted in a wire myograph for isometric tension recordings. Rings were precontracted with 21% O2, norepinephrine (NE, 1 μM) or KCl (62.5 mM).Results: MgSO4 (2.4-7.2 mM) elicited a concentration-dependent relaxation (mean maximal relaxation: 56.7%, SD 41.8; EC50: 2.9 mM, SD 0.3) of O2-induced active tone in E19 DA rings. MgSO4 also relaxed NE-contracted (with similar efficacy but lower potency than O2-contracted) and KCl-contracted (with lower efficacy and potency) E19 DA rings. MgSO4-induced relaxation of KCl-contracted DA rings was not significantly different between E15 and E19. Endothelium removal or the presence of the NO synthase inhibitor L-NAME, the soluble guanylate cyclase inhibitor ODQ, the cyclooxygenase inhibitor indomethacin, or the sarcoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin did not significantly modify MgSO4-induced relaxation. The relaxant effect of MgSO4 was reversed by increasing the extracellular Ca2 concentration.Conclusions: MgSO4, at clinically relevant concentrations, induces endothelium-independent relaxation of chicken DA. This relaxant effect may be due to inhibition of Ca2+ entry from extracellular space.
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