EFFECTS OF ANTIMONY ON THE CARDIOVASCULAR SYSTEM AND INTESTINAL SMOOTH MUSCLE

¹ Department of Pharmacology, University of Oklahoma School of Medicine, Oklahoma City, Oklahoma

Repeated daily injections of antimony potassium tartrate (tartar emetic) and sodium antimony dimercaptosuccinate (TWSb) had little effect upon the diastolic blood pressure of conscious dogs, although TWSb decreased the systolic pressure after 4 or 5 days of treatment. Both antimonials increased heart rate progressively during these experiments. Dogs receiving tartar emetic died after 3 to 5 days of treatment, while dogs receiving TWSb died only after 5 to 7 days of treatment. Geometrically increasing doses of the antimonials given to anesthetized dogs lowered blood pressure and increased heart rate progressively. Cardiac contractile force was variably affected, and the changes in this parameter were influenced by the fall in blood pressure, the reflex sympathetic stimulation caused by the fall in pressure and the direct depressant action of large doses of the antimonials. The cardiac responses to norepinephrine, isoproterenol and tetramethylammonium bromide (TMA) were essentially unaffected by tartar emetic and TWSb, but the pressor responses to norepinephrine and TMA and the depressor responses to acetylcholine, histamine and isoproterenol were progressively reduced as the systemic blood pressure fell. These reductions in vascular reactions were apparently not the result of a decrease in the sensitivity of the vascular smooth muscle, since the effects of norepinephrine, acetylcholine and histamine were essentially unaffected, even by large doses of the antimonials, when injected intraarterially in the perfused hind limb of the dog. Large doses of tartar emetic, but not TWSb, caused slowing of the heart which on occasion simulated that which can be evoked by electrical stimulation of the right vagus nerve. This bradycardia could not be shown to be the result of an enhanced sensitivity of the heart to vagal stimulation. The bradycardia caused by tartar emetic probably resulted from the high concentration of potassium, since equal concentrations of potassium alone decreased the contraction frequency of spontaneously contracting right atria to approximately the same extent as tartar emetic. Further, TWSb and sodium antimony tartrate had little influence on contraction frequency in similar experiments. Experiments with isolated heart muscle of the guinea pig revealed that tartar emetic and TWSb have little depressant action on the contractile force of the heart or its responses to norepinephrine until extremely high concentrations are reached. Similarly, the aortic smooth muscle and its responses to norepinephrine are relatively unaffected by the antimonials. However, the smooth muscle of the guinea pig ileum is contracted by low concentrations of both tartar emetic and TWSb. This contraction appeared to be, at least partially, cholinergic in nature since it was readily reduced by atropine, although this conclusion can only be tentative at present.