Functional role of sodium pump in human placental arteries.
Ouabain (10(-7) to 10(-4) M) elicited concentration-dependent contractile responses in human placental arteries. The contractions were reduced by 10(-4) M amiloride and Ca(2+)-free medium, but not affected by 10(-6) M nifedipine or 10(-6) M Bay-K-8644, which markedly reduced or potentiated 75 nM K(+)-induced contractions, respectively. After contracting the vessels with 10(-6) M prostaglandin F2 alpha in a K(+)-free medium, the subsequent addition of 7.5 mM K+ induced a marked relaxation, which was blocked by 10(-6) M ouabain. This glycoside (10(-8) to 10(-4) M) also produced a concentration-dependent reduction of 86Rb+ uptake. Scatchard analysis of the [3H]-ouabain binding to membrane fractions from human placental arteries suggests a single class of binding sites with a KD of 88.3 nM and a Bmax of 345 fmol/mg. 5-Hydroxytryptamine (5-HT; 10(-9) to 10(-5) M) caused concentration-dependent contractions. Single concentrations produced transient responses composed of an initial contraction, followed by a slow fall in tension. Ouabain (10(-8) to 10(-6) M), K(+)-free medium or the reduction of bath temperature (28 degrees C) did not modify contractions but inhibited the relaxant phase of the response. 5-HT (10(-8) to 10(-6) M) increased both total and ouabain-insensitive 86Rb+ uptake, but the difference between them was not modified. These data indicate that: (1) human placental arteries possess an important sodium pump activity, inhibition or stimulation of which markedly alters vascular tone, (2) ouabain-evoked contractions are produced by Ca2+ entry mainly through Na(+)-Ca2+ exchange, secondary to intracellular Na+ accumulation, (3) the relaxant component of 5-HT response is dependent on the activity of the sodium pump, (4) the activation of Na+,K(+)-ATPase activity by this amine is not apparently due to direct effect, and (5) the inhibition of the sodium pump can cause long lasting increases of placental vascular resistance in the presence of physiological concentrations of 5-HT.
Fernández-Alfonso
M S
MS
Departamento de Farmacologia y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Sánchez-Ferrer
C F
CF
Salaices
M
M
Marín
J
J
D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply* / Q000187:drug effects; D011247:Pregnancy; D012413:Rubidium / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
D002120:Calcium Channel Agonists; D012701:Serotonin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium