Endothelial modulation of the ouabain-induced contraction in human placental vessels.
Ouabain (1 x 10(-7)-3 x 10(-5) M) elicited concentration-dependent vasoconstriction in human placental arteries and veins. These responses, but not those produced by 10(-6) M 5-hydroxytryptamine, were increased after the removal of vascular endothelium. In placental arteries, the respective blockade of cyclooxygenase or lipoxygenase with indomethacin of 5,8,11,15-eicosatetraynoic acid as well as the inactivation of nitric oxide with phenidone or oxyhemoglobin and the inhibition of nitric oxide synthesis with NG-monomethyl L-arginine (all at 10(-5) M) did not mimic the effects of endothelial denudation on ouabain-evoked contractions. Bioassay experiments suggested that the above-mentioned endothelial effects are mediated by diffusible factors. 86Rb+ uptake, a method to measure sodium pump activity, was significantly reduced by the removal of endothelium. These results suggest the existence of an inhibitory modulation by the endothelium of the contractions induced by ouabain, likely mediated by a diffusible factor(s) released from these cells. The nature of this substance is unknown but is not related to prostaglandins or leukotrienes, and neither is it a nitric oxide-related compound. Its mechanism of action could be stimulating the activity of vascular sodium pump and/or antagonizing its inhibition by ouabain.
Sánchez-Ferrer
C F
CF
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Fernández-Alfonso
M S
MS
Ponte
A
A
Casado
M A
MA
González
R
R
Rodríguez-Mañas
L
L
Pareja
A
A
Marín
J
J
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives; D001158:Arteries / Q000187:drug effects; D001681:Biological Assay; D001808:Blood Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology*; D010108:Oxyhemoglobins / Q000032:analysis; D010920:Placenta / Q000098:blood supply*; D011720:Pyrazoles / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins / Q000187:drug effects; D019323:omega-N-Methylarginine
D016859:Lipoxygenase Inhibitors; D010108:Oxyhemoglobins; D011720:Pyrazoles; D015117:5,8,11,14-Eicosatetraynoic Acid; D019323:omega-N-Methylarginine; D010042:Ouabain; D001120:Arginine; D012964:Sodium; C015429:phenidone; D007213:Indomethacin