EFFECT OF GUANETHIDINE AND BRETYLIUM ON HEART RATE RESPONSES TO THYROXINE

¹ Department of Pharmacology, University of Vermont College of Medicine, Burlington, Vermont

Rats were given guanethidine or bretylium at a dosage of 15 mg per kg per day, reported by others to cause sympathetic blockade. By 4 days, guanethidine had decreased the mean heart rate 40 beats per minute, whereas bretylium had no effect.

At this time, the animals were injected with thyroxine (T₄) , 100 µg per kg per day, in addition to saline, guanethidine or bretylium. The heart rates increased in all instances, but the guanethidine-T₄ increase attained a level only 75% of that of the controls given T₄ , while the bretylium-T₄ was 60%. The latter value was statistically different from the control increase, while the guanethidine was not.

The heart norepinephrine levels were dropped to 25% of the controls by guanethidine, but were unchanged by bretylium. Typical thyroxine-induced increases in heart weight and adrenal weight were obtained in the animals also receiving the blocking agents.

It is concluded that guanethidine and bretylium do not eliminate the peripheral effects of T₄, although they may diminish responses.