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Title: Cardiovascular effects of serotonergic agents
Author: Hood, Stuart Hugh Macpherson
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1999
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Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter which exerts its cardiovascular effects predominantly by interaction with specific 5-HT1 and 5- HT2 receptors. The effects of serotonergic agents differ between in vivo and in vitro preparations and display wide inter-species variation. It is therefore impossible to extrapolate results from animal or in vitro studies to the clinical situation. The role of these two receptors has therefore been studied in patients with suspected coronary artery disease using 3 different 5-HT1 agonists and ketanserin, a 5-HT2 antagonist. Sumatriptan and naratriptan, 5-HT1B/D receptor agonists, vasoconstrict the systemic and pulmonary circulations. Sumatriptan-induced vasoconstriction appears more pronounced in the pulmonary circulation suggesting a greater density of 5-HT1 receptors in the pulmonary compared to the systemic circulation. Although left ventricular end diastolic pressure and pulmonary artery wedge pressure rose after sumatriptan, there was no change in peak rate of left ventricular pressure rise, indicating the absence of a negative inotropic action. Naratriptan, an analogue of sumatriptan, displayed no significant effect on coronary artery diameter, a finding previously noted with sumatriptan. Eletriptan, a selective 5-HT1D agonist with less 5-HT1B activity, had little vasoconstrictor effect on the systemic, pulmonary or coronary circulation perhaps suggesting that the 5-HT1B receptor subtype mediates vasoconstriction. The effect of sumatriptan on systolic time intervals and forearm blood flow was also assessed. The results suggest that STI's are of potential use in the non-invasive assessment of 5-HT1 agonists. No significant effect on forearm blood flow was observed but plasma noradrenaline levels fell after subcutaneous sumatriptan. Ketanserin, a 5-HT2 antagonist, acted as a vasodilator in the systemic and pulmonary circulation but failed to vasodilate the coronary arteries, presumably because the patients in this study had stable angina without platelet activation and therefore had low circulating levels of serotonin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available