VASOACTIVITY OF MAGNESIUM SULFATE IN CHICKEN DUCTUS ARTERIOSUS

Prenatal treatment with magnesium sulfate (MgSO4) has neuroprotective effects in very preterm infants but its use has been associated with an increased rate of patent ductus arteriosus (DA). MgSO4 is a vasodilator and thus may exert a direct relaxant effect in the DA. We aimed to investigate the vasoactive effects of MgSO4 in the DA using the chicken embryo as experimental model. DA rings from 15-d (E15), 17-d (E17) and 19-d (E19) chicken embryos (total incubation: 21-d) were mounted in a wire myograph for isometric tension recordings. Exposure of DA rings to 21% O-2 induced a tonic contraction which was relaxed by MgSO4 (2.4 - 7.2 mmol L-1) in a concentration-dependent manner (mean maximal relaxation E19: 51.4%, SE 6.3; EC50: 3.5 mmol L-1, SE 0.7). The relaxation evoked by MgSO4 was not significantly different between E15, E17 and E19 DA and was not affected by removal of the endothelium or by the presence of the nitric oxide synthase inhibitor L-NAME, the soluble guanylate cyclase inhibitor ODQ, or the cyclooxygenase inhibitor indomethacin. In contrast, when the DA rings were incubated in Ca2+-free solution, or in the presence of inhibitors of L-type Ca2+ channels (nifedipine), or large-conductance Ca2+-activated K+ (BKCa) channels (iberiotoxin), MgSO4-induced relaxation was impaired. Preincubation of the DA rings with MgSO4 concentrations ranging from 0 to 6.0 mmol L-1 did not significantly affect O-2-induced contraction that was only impaired by a concentration of 7.2 mmol L-1. In conclusion, MgSO4 induced endothelium-independent relaxation of chicken DA and this relaxation appeared to be mediated through stimulation of BKCa channels and blockade of transmembrane flux of extracellular Ca2+. However, O-2-induced DA contraction was only impaired by suprapharmacological concentrations of MgSO4 (> 6.0 mmol L-1). Therefore, our data suggest that the higher incidence of patent DA in preterm infants exposed to MgSO4 is unlikely to be due to a direct pharmacological effect of the drug on the DA.