Dando, Simon Burke; (1995) The role of 5-hydroxytryptamine receptors in the reflex activation of cardiac vagal motoneurones in the anaesthetised rabbit and rat. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

There is indirect evidence in the literature that activation of 5-HT receptors can modulate vagal control of the heart. The experimental work carried out in this thesis has examined the possibility that cardiac-vagal respiratory responses evoked by stimulating upper airway receptors with smoke, and by the pulmonary C-fibre reflex elicited by i.v. phenylbiguanide (PBG) are modulated by 5-HT pathways. This was done in anaesthetised rabbits and rats by i.e. administration of 5-HT receptor agonists and antagonists. Measurements were made of blood pressure, R-R interval, phrenic nerve activity and renal nerve activity. In rabbits reflex responses to the above stimuli were inhibited by 5-HT1A antagonists i.e. and potentiated by the 5-HT1A agonist buspirone i.e. Pretreatment with a 5-HT1A antagonist blocked the effect of buspirone. Administration of the 5-HT1D agonist sumatriptan i.e. inhibited the smoke response and the 5-HT1D antagonist GR-127935 i.c. potentiated it. Pretreatment with GR-127935 i.v. blocked the 8-OH-DPAT i.e. inhibition of the smoke response. Administration of a 5-HT3 antagonist, granisetron i.e. inhibited the response to smoke. Rats showed a species difference in that 5-HT1A agonists caused an inhibition of the smoke response that could be blocked by pretreatment with a 5-HT1A antagonist, WAY- 100802 i.e. and administration of 5-HT1A antagonists i.e. alone did not affect the reflex responses to smoke or PBG in the rat. Administration of granisetron also did not affect the smoke response. It is therefore concluded that in rabbits activation of central 5-HT1A receptors potentiate reflex activation of cardiac vagal motoneurones whilst these reflexes are inhibited by activation of 5-HT1D receptors. In contrast, central 5-HT3 receptors exert excitatory control over transmission of the reflexes. There is evidence for a species difference between rabbits and rats.

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