Neurogenic Component of Ouabain-Evoked Contractions Is Modulated by the Endothelium

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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 μmol/L to 0.1 mmol/L) evoked concentration-dependent increases of perfusion pressure. Phentolamine (0.3 to 10 μmol/L) and prazosin (30 nmol/L to 10 μmol/L) (nonselective antagonist of α-adrenergic receptors and selective antagonist of α1,-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 μmol/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. Deendothelialization abolished the effect of adrenergic blockade on ouabain-induced contractions. On the other hand, deendothelialization did not modify significantly the effect of the adrenergic blockade on norepinephrine-induced contractions. The nitric oxide blocker oxyhemoglobin, at concentrations (10 μmol/L) that abolished endothelium-dependent relaxations induced by 3 μmol/L acetylcholine, or the cyclooxygenase blocker indomethacin (10 μmol/L) did not modify the relaxation caused by phentolamine. In bioassay experiments, 30 μmol/L phentolamine induced a relaxation on the ouabainelicited 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 μmol/L oxyhemoglobin or 1 μmol/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.

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