Analysis of the tachycardiac response to 5-hydroxytryptamine in the spinal guinea-pig

The mechanism of the increase in heart rate caused by 5-hydroxytryptamine (5-HT) in the spinal guinea-pig was investigated. Administration of 5-HT (15, 30, 60 and 120 micrograms.kg-1 i.v.) elicited dose dependent increases in heart rate. The responses to 5-HT were not modified by methiothepin (0.5 and 1.5 mg.kg-1), ketanserin (0.5-4.5 mg.kg-1) or MDL 72222 (0.5-4.5 mg.kg-1) but were antagonized by the beta-adrenoceptor antagonists, propranolol (0.1-1 mg.kg-1) or atenolol (0.5-4.5 mg.kg-1). Indalpine, which is known to interfere with the uptake of 5-HT by nerve terminals and blood platelets, significantly reduced the effects of 5-HT at a dose (5 mg.kg-1) that also affected the tachycardia elicited by tyramine. The increase in heart rate caused by tyramine in reserpinized animals was attenuated and, unlike normal animals where the responses to 5-HT remained constant after repeated administration, there was a quickly developing tachyphylaxis to 5-HT. These results show that the increase in heart rate elicited by 5-HT in spinal guinea-pigs is not mediated by any of the currently characterized 5-HT receptors ('5-HT1-like', 5-HT2 and 5-HT3), and that a major part of the tachycardia seems to be mediated by a release of catecholamines by a mechanism similar, though perhaps not identical, to that for tyramine. Another as yet unidentified mechanism could be involved besides though perhaps not identical, to that for tyramine. Another as yet unidentified mechanism could be involved besides this action.