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 oxide in the vasorelaxant effect of magnesium sulfate during pregnancy.


METHODS
Segments of 3 mm of the aorta, with or without intact endothelium, 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 cumulative concentration-response curves for magnesium were determined after incubation with various inhibitors.


RESULTS
Magnesium relaxed the aortic rings from pregnant rats in a concentration-dependent manner. The relaxation was significantly lower on day 22 of gestation than on day 16 of gestation. Removal of the endothelium or incubation with 10(-4)-mol/L N omega-nitro-L -arginine methyl ester (a nitric oxide synthase inhibitor), 10(-5)-mol/L 6-anilino-5,8-quinolinedione (a guanylate cyclase inhibitor), or 10(-5)-mol/L indomethacin (a cyclooxygenase inhibitor) significantly decreased the relaxant effect of magnesium on aortic rings from 16-day-pregnant but not 22-day-pregnant rats. Treatment with minimally effective concentrations of a nitric oxide donor (3 x 10(-10)-mol/L sodium nitroprusside) or a cyclic guanosine monophosphate analog (10(-6)-mol/L 8-bromo-cyclic guanosine monophosphate) restored the response to magnesium.


CONCLUSIONS
The relaxant effect of magnesium on rat aortic rings was dependent on both endothelium and gestational age and was lower at term than during late pregnancy. The endothelium appears to potentiate the vasorelaxant effects of magnesium through the nitric oxide-cyclic guanosine monophosphate and cyclooxygenase systems.
Longo
M
M
Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas 77555-1062, USA.
Jain
V
V
Vedernikov
Y P
YP
Facchinetti
F
F
Saade
G R
GR
Garfield
R E
RE
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008278:Magnesium Sulfate / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000634:Aminoquinolines; D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D008278:Magnesium Sulfate; C041715:6-anilino-5,8-quinolinedione; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin