Abstract

Arterial blood inflow was measured in the dog's hind leg skeletal muscle with an electromagnetic flowmeter. Two technics were used to perfuse the leg. In technic I all collateral communications were obliterated, all nerves were severed and the bed was perfused with the animal's blood via a constant perfusion pressure system. In technic II the dissection was similar to the preceding but the proximal tourniquets were omitted; the sciatic and femoral nerves were preserved, the lumbar sympathetic chain was prepared for stimulation, and the vascular bed was autoperfused at the animal's own systemic blood pressure. Essentially equivalent data were obtained with both technics.

Small (0.03 to 0.1 mg/kg) doses of Dibozane converted the epinephrine response to vasodilation but only reduced the constrictor response to levarterenol (technic I) and to lumbar sympathetic nerve stimulation (technic II A). Larger doses (1 to 3.0 mg/kg) converted the levarterenol responses to vasodilation, which varied in magnitude up to one-half of that induced by epinephrine, but did not block completely the constrictor responses to the nerve stimulation. The largest dose of Dibozane (10 mg/kg) did not modify further the responses to epinephrine and levarterenol.

The doses required to induce the various levels of blockade were similar for Dibozane and phenoxybenzamine; the corresponding doses of azapetine were 3 to 30 times those of Dibozane for levarterenol and 2 to 3 times those of Dibozane for epinephrine. Epinephrine reversal persisted with the largest dose of Dibozane but disappeared with the largest doses of phenoxybenzamine and azapetine.

All three blocking drugs became relatively more potent the larger the dose of the adrenergic agent, thus the blocking action of all three appeared to be noncompetitive.

After a single dose of 0.5 mg/kg of Dibozane the constrictor responses to levarterenol were almost abolished and prominent dilator responses to nerve stimulation were unmasked. Approximately 2 hours and 30 minutes (B50 time) were required for the responses to levarterenol and to nerve stimulation to return half way to the control level on a logarithmic scale (B50 response). In the same experiments the B50 response for epinephrine occurred at 5 hours.

The type and duration of the blockade induced by 0.5 mg/kg of azapetine were almost identical to those of Dibozane.

After 0.5 mg/kg of phenoxybenzamine the B50 responses of levarterenol and nerve stimulation were reached in approximately 6 hours while the B50 response for epinephrine was not reached when the experiments were terminated at 8 hours and 50 minutes after the injection of the phenoxybenzamine. These B50 times were significantly longer than those for Dibozane and azapetine.

During single intraarterial infusion of 0.5 mg/kg of each of the three agents, marked vasodilation with increase in blood flow occurred in the skeletal muscle bed without change in systemic arterial pressure. Subsequently the blood pressure fell with all agents. The increase in conductance was transient with Dibozane and azapetine whereas with phenoxybenzamine the conductance remained increased sufficiently to more than compensate for the decline in arterial pressure so that the flow remained elevated.

Based on these studies it appears that an adequate clinical trial of Dibozane is warranted in vasospastic and other peripheral vascular diseases and as a test for pheochromocytoma.