CLONIDINE AND RILMENIDINE SUPPRESS HYPOTENSION-INDUCED FOS EXPRESSIONIN THE LOWER BRAIN-STEM OF THE CONSCIOUS RABBIT

Our current knowledge of the sites of action of the centrally-acting a ntihypertensive drug clonidine is based almost entirely on experiments in anesthetized animals. The aim of this study was to determine, in c onscious 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, hypo tension was produced by continuous intravenous infusion of sodium nitr oprusside, at a rate sufficient to decrease arterial pressure by 20-30 mmHg, maintained for a period of 60 min. In the second and third grou ps of experiments, sustained hypotension was also produced by nitropru sside infusion as in the first group, but this was preceded by intrave nous injection of clonidine (7-30 mu g/kg i.v.) or rilmenidine (150-30 0 mu g/kg i.v.), respectively. In confirmation of our previous study [ Li Y.-W. and Dampney R. A. L. (1994) Neuroscience 61, 613-634], hypote nsion produced by nitroprusside alone induced a large increase (compar ed to sham control experiments) in the neuronal expression of Fos (a m arker of neuronal activation) in the nucleus of the solitary tract, ar ea postrema, the rostral, intermediate and caudal parts of the ventrol ateral medulla, A5 area, locus coeruleus and subcoeruleus, and parabra chial nucleus. In comparison with this group, in rabbits pretreated wi th clonidine the numbers of Fos-positive cells were greatly reduced (b y 76-94%) in the rostral, intermediate and caudal parts of the ventrol ateral medulla, area postrema, A5 area, locus coeruleus and subcoerule us. Clonidine pretreatment also caused a more moderate reduction (by 4 5%) in the number of Fos-positive cells in the nucleus of the solitary tract, but had no effect on Fos expression in the parabrachial nucleu s. Double-labeling for tyrosine hydroxylase and Fos immunoreactivity s howed 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 brainste m, with a very similar pattern to that observed after clonidine pretre atment. The results indicate that in conscious animals both clonidine and rilmenidine cause a widespread but selective inhibition of neurons in the pens and medulla that are normally activated by a hypotensive stimulus. In contrast to previous observations in anesthetized animals , the results suggest that (i) systemic administration of both drugs i nhibits non-catecholamine as well as catecholamine neurons in the vent rolateral medulla, and (ii) the regional pattern of neuronal inhibitio n following administration of equipotent hypotensive doses of both dru gs is very similar.