Endothelial modulation of the vascular sodium pump.
Endothelial interference with ouabain effects on vascular smooth muscle was analyzed in isolated human placental arteries and veins, carotid arteries from reserpinized guinea pigs (to eliminate the adrenergic actions of the glycoside), and aorta from Wistar-Kyoto (WKY) rats that were 5 weeks, 3, 6, 12, and 18 months old. After endothelium removal, ouabain-evoked contractions were increased in human placental vessels and guinea pig carotid arteries. These effects were not mimicked by the blockade of nitric oxide, prostaglandin, or leukotriene synthesis. Bioassay experiments suggest the release of an endothelial diffusable factor(s). 86Rb+ uptake, a method to measure sodium-pump activity, was significantly reduced by the removal of endothelium. In aortas from WKY rats, ouabain caused contractions that were increased with the age of animals until 12 months. Endothelium removal increased ouabain effects in vessels from animals of 3 and 6 months but not in older ages. These results suggest (a) that there is an inhibitory endothelial modulation of ouabain-induced vasoconstriction by the release of a diffusible factor(s); (b) that this substance is not related to nitric oxide, prostaglandins, or leukotrienes; (c) that its mechanism of action could be stimulating the activity of vascular sodium pump and/or antagonizing its inhibition by ouabain; and (d) that the endothelial modulation is lost in the elderly.
Sánchez-Ferrer
C F
CF
Departamento de Farmacología y Terapéutica, Facultad de Medicina de la Universidad Autónoma de Madrid, Spain.
Ponte
A
A
Casado
M A
MA
Rodríguez-Mañas
L
L
Pareja
A
A
González
R
R
Fernández-Alfonso
M S
MS
Redondo
J
J
Marín
J
J
D000375:Aging / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply; D051381:Rats; D011921:Rats, Inbred WKY; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*
D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase