Inhibition of the 5-HT-induced cardiogenic hypertensive chemoreflex by the selective 5-HT3 receptor antagonist ICS 205-930 |
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Authors: | Heiner Berthold Günter Scholtysik Günter Engel |
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Affiliation: | (1) Preclinical Research, Sandoz Ltd., CH-4002 Basel, Switzerland |
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Abstract: | Summary We investigated the effect of ICS 205-930 [(3 -tropanyl)-1H-indole-3-carboxylic acid ester], a selective antagonist at 5-HT3 receptors, on the cardiogenic hypertensive chemoreflex in the anaesthetized dog. The reflex was elicited by injection of 5-HT (12.5–1600 g) into the left cardiac ventricle and consisted of a dose-dependent systemic hypertension associated with a decrease in heart rate. ICS 205-930 (10, 30, and 100 g/kg i.v.) caused a displacement to the right of both the dose-response curves of 5-HT-induced blood pressure increase and heart rate reduction. Its blocking effects upon the action of 5-HT could be surmounted by increasing the dose of the agonist. The selective 5-HT2 receptor antagonist, ketanserin (0.1 mg/kg i.v.) and the combined 5-HT1 and 5-HT2 receptor antagonist, methiothepin (0.1 mg/kg i.v.) had no influence on the hypertensive reflex. When the reflex was elicited by the ganglionic stimulant, 1,1-dimethyl-4-phenyl-piperazinium (DMPP; 100–1600 g), ICS 205-930 had no blocking effect. The results suggest that the 5-HT-induced cardiogenic hypertensive chemoreflex is mediated by 5-HT3 receptors.Send offprint requests to H. Berthold at the above address |
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Keywords: | Cardiogenic hypertensive chemoreflex 5-HT3 receptors 5-HT3 receptor antagonists Dog |
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