Endothelium dependence and gestational regulation of inhibition of vascular tone by magnesium sulfate in rat aorta

OBJECTIVE: The aim of this study was to investigate the role of nitric oxid e in the vasorelaxant effect of magnesium sulfate during pregnancy. STUDY DESIGN: Segments of 3 mm of the aorta, with or without intact endothe lium, from 16- or 22-day pregnant rats were mounted in organ chambers with standard Krebs solution or low-magnesium Krebs solution for measurement of isometric tension. The rings were contracted with phenylephrine, and cumula tive concentration-response curves for magnesium were determined after incu bation with various inhibitors. RESULTS: Magnesium relaxed the aortic rings from pregnant rats in;a concent ration-dependent manner. The relaxation was significantly lower on day 22 o f gestation than on day 16 of gestation. Removal of the endothelium or incu bation with 10(-4)-mol/L N-n omega itro-L-arginine methyl ester (a nitric o xide synthase inhibitor), 10(-5)-mol/L 6-anilino-5,8-quinolinedione (a guan ylate cyclase inhibitor), or 10(-5)-mol/L indomethacin (a cyclooxygenase in hibitor) significantly decreased the relaxant effect of magnesium on aortic rings from 16-day-pregnant but not 22-day-pregnant rats. Treatment with mi nimally effective concentrations of a nitric oxide donor (3 x 10(-10)-mol/L sodium nitroprusside) or a cyclic guanosine monophosphate analog (10(-6)-m ol/L 8-bromo-cyclic guanosine monophosphate) restored the response to magne sium. CONCLUSIONS: The relaxant effect of magnesium on rat aortic rings was depen dent on both endothelium and gestational age and was lower at term than dur ing late pregnancy. The endothelium appears to potentiate the vasorelaxant effects of magnesium through the nitric oxide-cyclic guanosine monophosphat e and cyclooxygenase systems.