Importance of Central Serotonin Neurons in the Hypotensive Action of Methyldopa in the Rat

Choy, V. J.; Chalmers, John

doi:10.1111/j.1440-1681.1984.tb00237.x

Cited by 10 publications

(4 citation statements)

References 21 publications

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“…Furthermore, these results are consistent with our recent demonstration that intraperitoneal administration of methyldopa can induce a green fluorescence typical of catecholamine fluorescence in serotonin cell bodies in the brain stem ( Figure 3A-C). 6 In these experiments too, the methyldopa-induced green fluorescence manifested by the Faglu method was abolished by pretreatment with 5,7-DHT ( Figure 3D). 6 While the mechanism by which methyldopa acts on central serotonin neurons to lower blood pressure is not yet defined, it is well established that methyldopa does deplete serotonin stores by inhibiting the enzyme L-aromatic amino acid decarboxylase, or "dopa-decarboxylase.""…”

Section: Icv Injectionmentioning

confidence: 63%

“…6 While the mechanism by which methyldopa acts on central serotonin neurons to lower blood pressure is not yet defined, it is well established that methyldopa does deplete serotonin stores by inhibiting the enzyme L-aromatic amino acid decarboxylase, or "dopa-decarboxylase."" It therefore seems possible that methyldopa might be taken up by serotonin neurons in the brain stem and is then decarboxylated to form methyldopamine, which in turn could be responsible for inducing the green fluorescence 6 and for lowering the arterial blood pressure.…”

Section: Icv Injectionmentioning

confidence: 99%

“…5 In addition, we have examined and compared the effects of microinjections of the hypotensive agent methyldopa into these ventrolateral areas of the medulla oblongata, as earlier studies have demonstrated that methyldopa is taken up extensively by serotonin cells in the brain stem. 6 Methods Adult male rats were used in these experiments. Rats used for histological studies were injected intraperitoneally (i.p.)…”

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Bulbospinal serotonin pressor pathways and hypotensive action of methyldopa in the rat.

Chalmers¹,

Minson²,

Choy³

1984

Hypertension

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SUMMARY The administration of methyldopa (200 mg/kg i.p.) induced a green fluorescence typical of catecholamine fluorescence, in regions of the brain stem which coincided with all the major serotonin cell groups, including the Bl, B2, and B3 cell groups in the medulla. Prior administration of 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin relatively specific for serotonin neurons, prevented the appearance of this methyldopa-induced fluorescence. Electrical stimulation of the ventrolateral medulla in areas that coincided with the lateral elements of the Bl and B3 serotonin cell groups evoked pressor responses recorded via cannulae in the abdominal aorta. The pressor responses were frequency-dependent and could be markedly attenuated by prior administration of 5,7-DHT either intracerebroventricularly (i.c.v.) or directly into the cervical cord to ablate descending serotonin nerve fibers. Microinjection of methyldopa (4-16 fxg) directly into the region of the Bl and B3 cells in the ventrolateral medulla evoked a dose-dependent fall in arterial pressure observed for 4 hours. Here too, prior administration of 5,7-DHT either intracerebroventricularly or directly into the cervical cord largely prevented the hypotensive action of the microinjections of methyldopa. The administration of 5,7-DHT produced a highly selective depletion of serotonin stores without reducing the concentrations of norepinephrine. These experiments suggest that the activity of serotonin nerves descending into the spinal cord from the Bl and B3 cells in the ventrolateral medulla serves to elevate or maintain arterial pressure. They also suggest that these descending serotonin neurons may contribute to the hypotensive action of methyldopa. 1 -2 This controversy has been aggravated by the tendency to treat the serotonin neurons as a homogeneous network subserving a single function and by a failure to recognize that there are numerous distinct serotoninergic projections with diverse roles in cardiovascular control.Recent studies from our laboratory have focused on the contribution of a single projection of serotonin neurons descending from the B1 and B3 groups in the caudal medulla and terminating in the intermediolateral cell column of the spinal cord.3 Although most groups of central serotonin cells are confined to the midline, the Bl and B3 groups have both a midline component and more lateral elements adjacent to the ventrolateral surface of the medulla oblongata as

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Section: Icv Injectionmentioning

confidence: 63%

Section: Icv Injectionmentioning

confidence: 99%

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confidence: 99%

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Bulbospinal serotonin pressor pathways and hypotensive action of methyldopa in the rat.

Chalmers¹,

Minson²,

Choy³

1984

Hypertension

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“…Ablation of central serotonin neurons by pretreatment with 5,7DHT attenuates the hypotensive effects of systemic administration of methyldopa [35]. Moreoever microinjection of methyldopa into the area of the lateral B3 serotonin cells also lowers blood pressure in a dose dependent manner, and this effect too is prevented by pretreatment with 5,7DHT [36].…”

Section: Central Serotonin Neurons and Antihypertensive Drugsmentioning

confidence: 92%

Central serotonergic mechanisms in cardiovascular regulation

Minson

Chalmers

Drolet

et al. 1990

Cardiovasc Drug Ther

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This paper reviews the role of central serotonin-containing neurons in the control of blood pressure. Central serotonin nerves have their cell bodies in the brainstem in a number of discrete collections, from where they ascend to ramify throughout the brain, descend to terminate in the spinal cord, or send shorter projections terminating in medulla, pons, and midbrain. Activation of one important ascending serotonin pathway innervating the preoptic region of the hypothalamus causes an increase in blood pressure. Activation of a bulbospinal serotonin projection descending from the ventrolateral medulla (the B3 cell group) to terminate in the intermediolateral cell column (IML) also evokes a pressor response. This pressor response is independent of that elicited by stimulation of the ventrolateral medulla in the adjacent but separate area containing the C1 adrenaline cell group. The pressor action appears to depend on increased release of serotonin, as detected by microdialysis in the area of the IML, and to be mediated by serotonin receptors of the 5HT1 subclass, probably located on sympathetic preganglionic neurons. It is possible that neuroactive excitatory amino acids, such as glutamate or aspartate, and neuropeptides such as substance P, also play a part in the pressor response evoked by stimulation of the ventrolateral medulla in the area of the lateral B3 serotonin cells. This descending serotonin pathway also appears important in mediating the hypotensive action of the antihypertensive drugs methyldopa and clonidine.

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Novel antihypertensive drugs — thoughts for the future

Laverty

1984

IUPHAR 9th International Congress of Pharmacology

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Importance of Central Serotonin Neurons in the Hypotensive Action of Methyldopa in the Rat

Cited by 10 publications

References 21 publications

Bulbospinal serotonin pressor pathways and hypotensive action of methyldopa in the rat.

Bulbospinal serotonin pressor pathways and hypotensive action of methyldopa in the rat.

Central serotonergic mechanisms in cardiovascular regulation

Novel antihypertensive drugs — thoughts for the future

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