Mediation of the hypotensive action of systemic clonidine in the rat by alpha 2-adrenoceptors. |
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Authors: | J P Hieble and D C Kolpak |
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Institution: | Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406. |
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Abstract: | 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 (I1 receptors) rather than from an alpha 2-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 affinity for both I1 and alpha 2-adrenoceptors; guanabenz represents a useful pharmacological tool, since it activates only the alpha 2-adrenoceptor. 3. Antagonists acting at both I1 and alpha 2-adrenoceptors (idazoxan) and at only alpha 2-adrenoceptors (SK&F 86466; 6-chloro-3-methyl-2,3,4,5-tetrahydro-3-benzazepine) are available. Idazoxan (1 mg kg-1, i.v.) and SK&F 86466 (3 mg kg-1, 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 alpha 2-adrenoceptor. 4. Guanabenz (30 micrograms kg-1, i.v.) and clonidine (10 micrograms kg-1, 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 alpha 2-adrenoceptors, with no significant contribution from an I1-mediated effect. Thus clonidine can lower blood pressure by different receptor mechanisms, dependent on the route of administration. |
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