COMPARISON OF THE CARDIOVASCULAR EFFECTS OF CENTRALLY ADMINISTERED CLONIDINE AND ADRENALINE IN THE ANESTHETIZED RAT

Intracerebroventricular (i.c.v.) injections of clonidine and adrenaline‐induced hypotension and bradycardia in urethane anaesthetized spontaneous hypertensive rats. The hypotension induced by clonidine (3 μg i.c.v.) was antagonized by pretreatment with the α‐antagonists piperoxan, which also antagonized clonidine‐induced bradycardia, and yohimbine. The hypotension and bradycardia induced by adrenaline (10 μg i.c.v.) were unaffected by α‐antagonist pretreatment, while β‐antagonist pretreatment with (‐(‐propranolol or metoprolol was effective against adrenaline but not clonidine‐induced hypotension and bradycardia. Pretreatments with the histamine H2‐receptor antagonists metiamide and cimetidine antagonized clonidine but not adrenaline‐induced hypotension. These data indicate that different central mechanisms are involved in mediating the hypotension and bradycardia induced by centrally administered clonidine and adrenaline and do not, therefore, support the hypothesis that the hypotensive effects of clonidine (i.c.v.) are mediated by central adrenaline receptor activation in urethane‐anaesthetized spontaneous hypertensive rats. 1979 Royal Pharmaceutical Society of Great Britain