THE EFFECT OF TWO DIOXANE DERIVATIVES, 883 AND 933F, ON NORMAL DOGS AND ON ANIMALS WITH NEUROGENIC AND RENAL HYPERTENSION

¹ From the Department of Medicine, the Johns Hopkins Hospital

1. The effect of the intravenous injection, infusion, and oral administration of two dioxane derivatives, 883 and 933F, on normal unanesthetized dogs, and on animals with chronic neurogenic hypertension, was studied. In addition, the action of 833F on animals with renal hypertension was observed.

2. In the normal animal, the injection of 933F produced transient hypertension; the infusion of this compound was without effect on the blood pressure, while its oral administration resulted in a slight fall. The heart rate increased after both intravenous and oral administration.

3. The intravenous injection and infusion of 883F into normotensive animals as well as the oral ingestion of this compound, was succeeded by a slight fall in blood pressure and by a significant increase in the heart rate.

4. The hemodynamic changes observed in normal animals during the infusion of 933 and 883F, consisted in a decline of the systolic discharge and an increase in the heart rate the minute volume was maintained or fell only slightly. The total peripheral resistance remained unchanged.

5. In animals with chronic neurogenic hypertension, the injection of 883 and 933F elicited a transient fall in blood pressure and an increase in the heart rate. The infusion of these compounds was followed by a decline in blood pressure, succeeded by a short period of hypertension with tachycardia. Toward the end of the infusion the heart rate and blood pressure declined. The oral administration of the two dioxanes resulted in a fall in blood pressure and a decrease in the heart rate, the effect persisting for several hours.

6. The hemodynamic alterations observed during the infusion of 933 and 883F into animals with sectioned moderator nerves consisted in a fall in systolic discharge, accompanied by a decrease in the pulse rate and in the minute volume.

7. The infusion of saline into animals with chronic neurogenic hypertension did not result in a prolonged decrease in the blood pressure or the heart rate.

8. The injection and infusion of 883F failed to lower the blood pressure of animals with chronic renal hypertension.

9. The possible application of these findings in the treatment of essential hypertension and in the differentiation of essential from renal hypertension is discussed.