Cardiovascular effects of calcitonin

Parker, J.E., 1989. Cardiovascular effects of calcitonin. PhD, Nottingham Trent University.

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Abstract

This thesis has examined the mechanisms underlying the pharmacological effects of salmon calcitonin (sCT), particularly the haemodynamic effects of the peptide in normotensive anaesthetised rats and those rendered hypotensive by haemorrhage, a situation in which sCT may be of potential therapeutic benefit.

Using biochemical techniques, sCT, administered centrally to urethane anaesthetised normotensive rats, was demonstrated to result in a trend for an increase in the concentrations of whole brain 5-hydroxytryptamine (5-HT) or 5-hydroxyindole acetic acid (5-HIAA).

Salmon CT, administered intravenously to anaesthetised rats subjected to endotoxin shock, was demonstrated to have no significant effect on blood pressure, but resulted in a decreased heart rate response in these rats. Conversely, salmon CT (iv) was shown to exert a pressor effect concomitant with an increased heart rate response in urethane anaesthetised rats subjected to haemorrhage, but was devoid of effect in urethane anaesthetised normotensive rats. The pressor effect was abolished and the increased heart rate response attenuated by peripheral sympathetic nervous system blockade. It is concluded that the pressor effect of iv sCT is mediated solely by the peripheral sympathetic nervous system, but that the increased heart rate response is only partly mediated by this system.

Centrally administered sCT has been demonstrated to exert a pressor effect concomitant with an increased heart rate response in both urethane anaesthetised normotensive rats and those rendered hypotensive by haemorrhage. Pharmacological and surgical procedures which interfered with the release of catecholamines from peripheral sympathetic neurones and the adrenal medullae and the function of the renin-angiotensin system were used to investigate these effects.

It is concluded that the release of catecholamines from peripheral sympathetic neurones and the adrenal medullae are equally responsible for the pressor effect of icv sCT in normotensive rats, but that the peripheral sympathetic nervous system is more important than the adrenal medullae in mediating the increased heart rate response to icv sCT. Conversely, the release of catecholamines from peripheral sympathetic neurones and the adrenal medullae as well as the vasoconstrictor effects of angiotensin II are involved in the pressor effect of icv sCT in haemorrhaged rats, although the peripheral sympathetic nervous system appears to play the major role. The peripheral sympathetic nervous system and the presence of intact adrenal medullae would appear to mediate the increased heart rate response to icv sCT in these animals.

The sites of action of peripherally and centrally administered sCT are discussed. The possible interaction of calcitonin gene-related peptide with receptors for CT is also discussed.

Item Type:	Thesis
Creators:	Parker, J.E.
Date:	1989
ISBN:	9781369314038
Identifiers:	Number Type PQ10183122 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Jeremy Silvester
Date Added:	18 Sep 2020 08:31
Last Modified:	19 Jul 2023 10:41
URI:	https://irep.ntu.ac.uk/id/eprint/40788

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