Clonidine and rilmenidine suppress hypotension-induced Fos expression in the lower braistem of the conscious rabbit

Y. W. Li, R. A L Dampney*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Our current knowledge of the sites of action of the centrally-acting antihypertensive drug clonidine is based almost entirely on experiments in anesthetized animals. The aim of this study was to determine, in conscious rabbits, the sites of action in the brainstem of systemically administered clonidine, as well as its oxazoline analog rilmenidine. Three groups of experiments were carried out. In the first group, hypotension was produced by continuous intravenous infusion of sodium nitroprusside, at a rate sufficient to decrease arterial pressure by 20-30 mmHg, maintained for a period of 60 min. In the second and third groups of experiments, sustained hypotension was also produced by nitroprusside infusion as in the first group, but this was preceded by intravenous injection of clonidine (7-30 μg/kg i.v.) or rilmenidine (150-300 μg/kg i.v.), respectively. In confirmation of our previous study [Li Y.-W. and Dampney R. A. L. (1994) Neuroscience61, 613-634], hypotension produced by nitroprusside alone induced a large increase (compared to sham control experiments) in the neuronal expression of Fos (a marker of neuronal activation) in the nucleus of the solitary tract, area postrema, the rostral, intermediate and caudal parts of the ventrolateral medulla, A5 area, locus coeruleus and subcoeruleus, and parabrachial nucleus. In comparison with this group, in rabbits pretreated with clonidine the numbers of Fos-positive cells were greatly reduced (by 76-94%) in the rostral, intermediate and caudal parts of the ventrolateral medulla, area postrema. A5 area, locus coeruleus and subcoeruleus. Clonidine pretreatment also caused a more moderate reduction (by 45%) in the number of Fos-positive cells in the nucleus of the solitary tract, but had no effect on Fos expression in the parabrachial nucleus. Double-labeling for tyrosine hydroxylase and Fos immunoreactivity showed that clonidine pretreatment greatly reduced the numbers of both catecholamine and non-catecholamine Fos-positive neurons. Rilmenidine pretreatment also greatly reduced Fos expression in the lower brainstem, with a very similar pattern to that observed after clonidine pretreatment. The results indicate that in conscious animals both clonidine and rilmenidine cause a widespread but selective inhibition of neurons in the pons and medulla that are normally activated by a hypotensive stimulus. In contrast to previous observations in anesthetized animals, the results suggests that (i) systemic administration of both drugs inhibits non-catecholamine as well as catecholamine neurons in the ventrolateral medulla, and (ii) the regional pattern of neuronal inhibition following administration of equipotent hypotensive doses of both drugs is very similar.

Original languageEnglish
Pages (from-to)391-402
Number of pages12
JournalNeuroscience
Volume66
Issue number2
DOIs
Publication statusPublished - 1995
Externally publishedYes

Keywords

  • NHS
  • normal horse serum
  • NTS
  • nucleus of the solitary tract
  • PBS
  • phosphate-buffered saline
  • SNP
  • sodium nitroprusside
  • TH
  • tyrosine hydroxylase
  • ventrolateral medulla
  • VLM

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