Contribution of catecholaminergic neurons of the dorsomedial and ventrolateral medulla oblongata to the hypotensive effect of clonidine in spontaneously hypertensive rats: in vivo voltammetric studies.
OBJECTIVE
Our previous electrochemical studies in the normotensive Wistar-Kyoto (WKY) rat showed a positive correlation between the hypotensive effect of low doses of clonidine (2-10 micrograms/kg intravenously) and inhibition of the activity of catecholaminergic neurons within the brainstem, and that this action was mediated by imidazoline-preferring receptors. In the present study the possibility of a relationship between the centrally mediated hypotensive effect of clonidine and the metabolic activity of catecholaminergic neurons of the ventrolateral and dorsomedial medulla oblongata was investigated in pentobarbital-anaesthetized spontaneously hypertensive rats (SHR).


METHODS
Neuronal metabolic activity was monitored by in vivo electrochemistry in the nucleus reticularis lateralis region of the ventrolateral medulla and in the nucleus tractus solitarii region of the dorsomedial medulla oblongata.


RESULTS
Hypotensive doses of intravenously administered clonidine (10 micrograms/kg) failed to inhibit the neuronal metabolic activity of the nucleus reticularis lateralis region; fivefold higher doses were required to inhibit these neurons. The low dose of clonidine (10 micrograms/kg) decreased the metabolic activity of the nucleus tractus solitarii region. Nevertheless, this effect did not appear to be correlated with a reduction in blood pressure and it was not attenuated by a prior central injection of idazoxan (5 nmol/kg intracisternally), which almost completely prevented the hypotensive and the neuronal inhibitory effects of clonidine in the nucleus reticularis lateralis region of the normotensive rat.


CONCLUSIONS
Both the site and the mechanism of the central hypotensive action of clonidine in the SHR appear to be different from those in normotensive control WKY rats.
Tibiriça
E
E
Laboratoire de Pharmacologie Cardiovasculaire et Rénale, CNRS URA 589, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Feldman
J
J
Bousquet
P
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D004563:Electrochemistry; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR
D002395:Catecholamines; D003000:Clonidine