The hypotensive action of two novel imidazolinic alpha-adrenergic agonists (ICI-106270 and UK-14304) with similar pharmacological properties to clonidine was shown in spontaneously hypertensive (SH) rats. The antihypertensive effect of the clonidine-type agents was prevented by either peripheral administration of the opiate antagonist naloxone or by intracerebroventricular (i.c.v.) injection with a specific antibody against human beta-endorphin (BEN). A dose-response relationship was found for the hypotensive effect of i.c.v. given BEN in SH rats, the low blood pressure being significantly reversed by further treatment with either naloxone or anti-beta h-endorphin. These data confirm and extend the notion of a BEN mediation in the antihypertensive action of clonidine-type alpha-adrenergic agonists in SH rats.
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