Differences between the prejunctional effects of phenylephrine and clonidine in guinea‐pig isolated atria

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Abstract
The prejunctional effects of clonidine and phenylephrine were studied in guinea-pig isolated atria by means of field stimulation of the sympathetic nerve terminals during the cardiac refractory period, in the presence of 1 .mu.M atropine. Clonidine (10-100 nM) produced a dose-dependent decrease in the stimulus-inotropic response curve; the IC50 [medium inhibitory concentration] for clonidine was increased .apprx. 70 times by the pretreatment of the preparations with 1 mM yohimbine. The effect of clonidine was not modified by 0.5 .mu.M prazosin. Unlike clonidine, phenylephrine (1-10 .mu.M) induced a statistically insignificant increase in the contractile force of preparations stimulated at 4 Hz. The inhibitory effect of phenylephrine (1-10 .mu.M) was partially prevented by either 1 .mu.M yohimbine or 0.5 .mu.M prazosin. It was antagonized to about the same degree as that observed with clonidine, by the pretreatment of the preparations with both 1 .mu.M yohimbine and 0.5 .mu.M prazosin. One component of the prejunctional effects of phenylephrine may be mediated by presynaptic .alpha.-adrenoceptors belonging to the .alpha.1-subtype.