MODIFICATION BY GUANETHIDINE OF THE CHRONOTROPIC ACTION OF SYMPATHOMIMETIC AMINES IN THE HEART-LUNG PREPARATION OF THE DOG PRETREATED WITH RESERPINE

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The effect of guanethidine on the chronotropic potency of sympathomimetic amines was studied in heart-lung preparations of dogs pretreated with reserpine, 0.5 mg/kg 48 and 24 hours prior to isolation of the heart, so as to deplete the intrinsic stores of catecholamines. In such hearts, guanethidine causes an acute supersensitivity of the pacemaker to norepinephrine and epinephrine. In the case of norepinephrine, this effect becomes noticeable above a dosage level of 1 mg of guanethidine. After 3 mg of guanethidine, there is a 5-fold increase in sensitivity to norepinephrine; a 10-fold increase is observed after 6 mg of guanethidine.

Guanethidine does not change the sensitivity

of the pacemaker to either Synephrine or phenylephrine. The chronotropic potency of ephedrine which is decreased after reserpine pretreatment is further diminished after guanethidine.

The average initial heart rate of 66 heart-lung preparations from normal dogs was 137.0 beats per minute (temperature range 37.5-39.2°C). In 56 heart-lung preparations from dogs pretreated with reserpine, the average initial heart rate was significantly reduced to 126.1 beats per minute (temperature range 38.0-39.3°C).