title: Neurogenic component of ouabain-evoked contractions is modulated by the endothelium.
abstract: The influence of endothelium on the neurogenic component of ouabain-induced contractions in isolated perfused guinea pig carotid arteries was analyzed. Ouabain (0.1 mumol/L to 0.1 mmol/L) evoked concentration-dependent increases of perfusion pressure. Phentolamine (0.3 to 10 mumol/L) and prazosin (30 nmol/L to 10 mumol/L) (nonselective antagonist of alpha-adrenergic receptors and selective antagonist of alpha 1-adrenergic receptors, respectively) induced a concentration-dependent relaxation in segments precontracted with ouabain (0.1 mmol/L). When the arteries were preincubated with those blockers (both at 3 mumol/L) or the animals were pretreated with reserpine, the contractions to the glycoside were diminished, indicating that they are partially mediated by norepinephrine release from adrenergic nerve endings. De-endothelialization abolished the effect of adrenergic blockade on ouabain-induced contractions. On the other hand, de-endothelialization did not modify significantly the effect of the adrenergic blockade on norepinephrine-induced contractions. The nitric oxide blocker oxyhemoglobin, at concentrations (10 mumol/L) that abolished endothelium-dependent relaxations induced by 3 mumol/L acetylcholine; or the cyclooxygenase blocker indomethacin (10 mumol/L) did not modify the relaxation caused by phentolamine. In bioassay experiments, 30 mumol/L phentolamine induced a relaxation on the ouabain-elicited contraction only when the glycoside was added through a donor segment with endothelium. Ouabain-induced tritiated norepinephrine release was significantly reduced by the removal of endothelium but not by 1 mumol/L oxyhemoglobin or 1 mumol/L indomethacin. These results suggest that the endothelium modulates the neurogenic component involved in contractions evoked by the glycoside by a diffusible factor (or factors) whose nature is unknown; however, the factor is neither nitric oxide nor a cyclooxygenase-related compound.
authors.affiliation: Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Rodríguez-Mañas
authors.forename: C F
authors.initials: CF
authors.lastname: Sánchez-Ferrer
authors.forename: A
authors.initials: A
authors.lastname: Pareja
authors.forename: M A
authors.initials: MA
authors.lastname: Casado
authors.forename: S
authors.initials: S
authors.lastname: Arribas
authors.forename: M
authors.initials: M
authors.lastname: Salaices
authors.forename: J
authors.initials: J
authors.lastname: Marín
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000294:innervation / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D010477:Perfusion; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D010042:Ouabain; D009638:Norepinephrine