Depressive action of clonidine on guinea pig and rabbit atrial pairs

The effects of clonidine, a compound used clinically as a centrally active antihypertensive, were studied on isolated, spontaneously beating atria of rabbit and guinea pig. In rabbit atria clonidine induces a marked depression of spontaneous chronotropic activity which was not altered by pretreatment with atropine, and not completely reversed by washing. In guinea pig atria, clonidine alone induces a very small increase in rate. A significant decrease in rate however is unmasked when tissues are pretreated with metiamide (H2-antagonist). Since both rabbit and guinea pig atria contain histamine receptors the lack of a positive chronotropic response in rabbit atria suggests that clonidine has no direct H2-receptor activity. The small positive response obtained with guinea pig atria which can be blocked by metiamide suggests that clonidine can act indirectly by releasing endogenous histamine stores from this tissue. Clonidines direct action appears to be a significant depression of both rabbit and guinea pig atrial chronotropic activity.