Brainstem neurons involved in the control of the cardiovascular system

Author: Paul Pilowsky

Pilowsky, Paul, 1987 Brainstem neurons involved in the control of the cardiovascular system, Flinders University, School of Medicine

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Abstract

Neurons that lie within the ventrolateral medulla have been implicated in the tonic and reflex control of the cardiovascular system. In this thesis the chemical content of these neurons, their effect on sympathetic outflow and the release of putative neurotransmitters from their terminals has been investigated.

Chemical stimulation and inhibition of the ventrolateral medulla revealed that the changes seen in blood pressure were associated with parallel changes in sympathetic nerve activity, suggesting that bulbospinal sympathoexcitatory pathways were responsible for mediating these effects. In addition it was found that the increase in blood pressure that follows anodal electrolytic lesions of the caudal ventrolateral medulla is closely associated with an increase in sympathetic nerve activity, suggesting that it is an increase in bulb,ospinal traffic that is responsible for these changes rather than an increase in plasma vasopressin.

The importance of serotonergic and catecholaminergic neurons in the brain in mediating changes in the activity of sympathetic nerves was assessed by recording sympathetic nerve activity, plasma vasopressin, adrenaline and noradrenaline, in response to intracisternal injections of the neurotoxins 6-hydroxydopamine and 5,7-dihydroxytryptamine. In both cases increases in sympathetic nerve activity were seen, although there was a differentiated response in terms of the changes in the levels of plasma hormones.

In chapters 5, 6 and 7 the release of putative neurotransmitters (neuropeptide Y and serotonin) from

the spinal cord was used as an index of the activity of spinally projecting pathways that utilise these

substances. Two methods were used, firstly the technique of in vivo tissue dialysis was adapted for

the measurement of serotonin in the thoracic spinal cord of the rat. Secondly, spinal subarachnoid space perfusion was used in the rabbit in order to measure the release of neuropeptide Y like immunoreactivity. It was found that stimulation of the serotonin-containing cells in the rostral ventrolateral medulla of the rat increased blood pressure and the release of serotonin from the spinal cord. Both the increase in arterial pressure and the release of serotonin were prevented by prior destruction of central serotonergic pathways with 5,7-dihydroxytryptamine. Similarly stimulation of the

rostral ventrolateral medulla of the rabbit elicited an increase in arterial pressure and the concentration of neuropeptide Y like immunoreactivity in the subarachnoid space. An increase in arterial pressure

and an increase in the release of neuropeptide Y- like immunoreactivity was also seen after inhibition of the caudal ventrolateral medulla, suggesting that the presser and depressor effects that can be elicited from the caudal ventrolateral medulla are due to changes in the activity of spinally - projecting neuropeptide Y - containing neurons of the rostral ventrolateral medulla.

In an attempt to determine whether or not the serotonin or neuropeptide Y containing neurons participate in the baroreflex control of blood pressure, the release of these compounds from the

spinal cord was measured before and after acute sinoaortic denervation in urethane anaesthetized

rabbits. Although this procedure resulted in an elevation of arterial pressure, there was no increase

in the release of either substance. Since on the other hand there was an increase in plasma vasopressin levels that could account for the increase in arterial pressure, it seems likely that acute sinoaortic denervation in this context is not a suitable stimulus of bulbospinal sympathoexcitatory pathways.

Finally, the localization of substance P and catecholamines within neurons of the ventrolateral

medulla was examined. It was found in the rat that the extent of colocalization of substance P with the

adrenaline synthesizing phenylethanolamine- N-methyl transferase was small, and dual labelled fibres were seen only rarely in the spinal cord. Similarly, no colocalization of substance P with catecholamine

fluorescent neurons was observed in the rabbit.

Keywords: Neurons, Sympathetic nervous system, Cardiovascular system

Subject: Medicine thesis

Thesis type: Doctor of Philosophy
Completed: 1987
School: School of Medicine
Supervisor: John Chalmers