Endothelial role in ouabain-induced contractions in guinea pig carotid arteries.
The influence of endothelium on the direct contractile effects of ouabain in vascular smooth muscle was analyzed in isolated perfused guinea pig carotid arteries. After blocking the neurogenic component of the glycoside contraction with alpha-adrenergic receptor blocking drugs or treating the animals with reserpine, ouabain-induced contractions were markedly reduced in vessels with intact endothelium. However, removal of the vascular endothelium from reserpinized carotid arteries resulted in ouabain-induced contractions similar to those observed in control arteries. These effects were not mimicked by the inhibitor of nitric oxide NG-monomethyl L-arginine or by the cyclooxygenase blocker indomethacin. Bioassay experiments suggested that these endothelial effects are mediated by diffusible factors. Uptake of 86Rb to measure sodium pump activity was significantly reduced by removal of the endothelium. These results suggest the existence of an inhibitory modulation by the endothelium of contractions induced by ouabain, likely mediated by a diffusible factor (or factors) released from these cells. The nature of this substance is unknown, but it is neither related to prostaglandins nor a nitric oxide-related compound. Its mechanism of action could be the stimulation of vascular sodium pump activity, the antagonism of the pump's inhibition by ouabain, or both.
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
L
L
Rodríguez-Mañas
A
A
Pareja
C F
CF
Sánchez-Ferrer
M A
MA
Casado
M
M
Salaices
J
J
Marín
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001681:Biological Assay; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D010477:Perfusion; D012110:Reserpine / Q000494:pharmacology; D012413:Rubidium / Q000493:pharmacokinetics; D014661:Vasoconstriction / Q000502:physiology*; D019323:omega-N-Methylarginine
D000317:Adrenergic alpha-Antagonists; D019323:omega-N-Methylarginine; D010042:Ouabain; D012110:Reserpine; D001120:Arginine; D012413:Rubidium; D007213:Indomethacin