1 During the past few years it has been shown that the sympatholytic effect resulting from localized microinjection of clonidine and other imidazolines into the rostral ventrolateral medulla (RVL) results from activation of 'imidazoline' receptors (I, receptors) rather than from an a2-adrenoceptor-mediated effect. 2 The relative contributions of these two receptor systems to the hypotensive action of systemically administered clonidine have not been studied. Clonidine has afffinity for both I1 and a2-adrenoceptors; guanabenz represents a useful pharmacological tool, since it activates only the a2-adrenoceptor. 3 Antagonists acting at both II and M2-adrenoceptors (idazoxan) and at only M2-adrenoceptors (SK&F 86466; 6-chloro-3-methyl-2,3,4,5-tetrahydro-3-benzazepine) are available. Idazoxan (1 mg kg-', i.v.) and SK&F 86466 (3 mg kg-', i.v.) produced an equivalent degree of blockade of the pressor response to guanabenz or clonidine in the pithed rat, a response mediated by the M2-adrenoceptor. 4 Guanabenz (30 gIg kg-', i.v.) and clonidine (10 jig kg-', i.v.) lowered blood pressure in the chloralose-anaesthetized spontaneously hypertensive rat by 48 ± 4.6 mmHg and 44 ± 5.4 mmHg, respectively; this response, for either agonist, was blocked by both idazoxan and SK&F 86466. 5 These data show that the hypotensive effect of intravenously administered clonidine results from activation of central M2-adrenoceptors, with no significant contribution from an 11-mediated effect. Thus clonidine can lower blood pressure by different receptor mechanisms, dependent on the route of administration.

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