Anderson, Ian Keith;
(1994)
The role of 5-hydroxytryptamine receptors in central cardiovascular regulation in rats and cats.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Administration of 5-hydroxytryptamine (5-HT) to the lateral cerebral ventricle of the rat and cat causes a pressor response. The physiological mechanism(s) and the nature of the 5-HT receptor(s) mediating this response are unknown. Using novel agonists and antagonists for 5-HT receptors, the subtypes of 5-HT receptors mediating the cardiovascular effects of intracerebroventricular (i.c.v.) administration of 5-HT were investigated in anaesthetized rats and cats, and in conscious Long-Evans (normal) and Brattleboro (vasopressin deficient) rats. Measurements were made of blood pressure, heart rate, sympathetic nerve activity and respiratory variables in anaesthetized preparations, while in conscious preparations (used to avoid anaesthetic- induced cardiovascular depression) blood pressure and heart rate were measured along with blood flows in the mesenteric, renal and hindlimb vascular beds using Doppler flow probes. In anaesthetized rats, 5-HT (i.c.v.) produced a pressor response associated with biphasic changes in heart rate and sympathetic nerve activity; bradycardia and sympathoinhibition were followed by tachycardia and sympathoexcitation. The sympathoinhibitory effects of 5-HT were blocked by 5-HT2/5-HT1C receptor antagonists (i.c.v.) and a vasopressin V1-receptor antagonist (i.v.) which unmasked immediate sympathoexcitation. 5-HT1A receptor agonists (i.c.v.) caused immediate increases in blood pressure, tachycardia and sympathoexcitation which were blocked by 5-HT1A receptor antagonists (i.c.v.). The response to 5-HT was abolished by combined 5-HT2/5-HT1C and 5-HT1A receptor blockade. In conscious rats, 5-HT caused a pressor response, bradycardia, mesenteric vasoconstriction and hindquarters vasodilatation. The mesenteric vasoconstriction and bradycardia were attenuated by a vasopressin V1-receptor antagonist (i.v.). In Brattleboro rats the mesenteric vasoconstriction caused by 5-HT was reduced compared to normal rats. In anaesthetized cats, 5-HT and a 5-HT2/5-HT1C receptor agonist (i.c.v.) caused an increase in blood pressure associated with femoral vasoconstriction, tachycardia and sympathoexcitation. The response to 5-HT was blocked by a 5-HT2/5-HT1C receptor antagonist (i.c.v.). In conclusion, in rats 5-HT caused a pressor response which was mediated in part, by the release of vasopressin following activation of central 5-HT2/5-HT1C receptors. This resulted in an initial bradycardia and sympathoinhibition due to activation of the baroreceptor reflex. 5-HT also caused sympathoexcitation following activation of central 5-HT1A receptors. In anaesthetized cats evidence suggests that the 5-HT-induced pressor response was mediated by activation of forebrain 5-HT2/5-HT1C receptors.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The role of 5-hydroxytryptamine receptors in central cardiovascular regulation in rats and cats |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Biological sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10103070 |
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