COMPARISON OF ADRENERGIC BLOCKING ACTION OF ILIDAR (Ro 2-3248), REGITINE (C-7337) AND PRISCOLINE IN THE INNERVATED SAPHENOUS ARTERIAL BED (SKIN EXCLUSIVE OF MUSCLE) AND FEMORAL ARTERIAL BED (MUSCLE EXCLUSIVE OF SKIN) OF THE ANESTHETIZED DOG

¹ Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest College, Winston-Salem, North Carolina

1. Cannulation of the femoral artery for muscle flow is accomplished by cannulating the ipsilateral femoral artery proximally and distally; vessels supplying skin areas were ligated. For skin flow the femoral artery and all branches of the saphenous found to supply muscle were ligated; the ipsilateral saphenous was then perfused by the proximal portion of the contralateral femoral artery. Clotting was controlled by intravenous injection of Treburon. Anesthesia was maintained with a mixture of Dial-urethane and sodium pentobarbital intravenously.

2. Flow was measured by an electromagnetic flowmeter in conjunction with an Esterline-Angus 5 milliampere recorder, properly calibrated for each experiment. Pressure was recorded immediately downstream from the flowmeter by a P-23A Stratham strain gage and a Brush strain analyser on an Esterline-Angus 5 milliampere recorder. Simultaneous pressure and flow recordings were used to calculate vascular bed resistance in PRU (PRU = pressure (mm. Hg)/flow (ml./min.)

3. Control intra-arterial injections of 1 microgm. of l-epinephrine, 1 microgm. of l-norepinephrine and 5 microgm. of phenylephrine each caused comparable vasoconstrictor effects in skin and muscle beds.

4. Following intra-arterial injection of 0.05 mgm./kgm. of Regitine and 0.3 mgm./kgm. of Priscoline or of Ilidar, intra-arterial injections of 1 microgm. of l-epinephrine casued vasodilation in muscle but still caused vasoconstriction in skin.

5. Following l-epinephrine reversal doses of the antiadrenergic drug intra-arterial injections of 1 microgm. of l-norepinephrine or 5 microgm. of phenylephrine still caused constriction in both skin and muscle beds, but of lesser magnitude.

6. A ten-fold increase in the dose of the blocking drugs, i.e., to 0.3 mgm./kgm. of Regitine or to 3.0 mgm./kgm. of Priscoline or of Ilidar caused blocking of the constrictor effect of all three adrenergic drugs in skin and of l-norepi-nephrine and phenylephrine in muscle; the dilator effect of l-epinephrine in muscle was unchanged.

7. Increase of the dose of the blocking drugs to ten times the norepinephrine and phenylephrine blocking dose, i.e., to 100 times the epinephrine reversal dose, blocked the dilator effect of l-epinephrine in muscle and continued to block all constrictor effects of all of the adrenergic drugs in the above mentioned doses in both skin and muscle without causing any further reversal.

8. The ratio of the doses of Ilidar and of Priscoline to Regitine remained the same for all three effects (epinephrine reversal, blocking of norepinephrine constriction, and blocking of epinephrine dilation in muscle); these were respectively approximately 10:10:1.

9. All doses of all three antiadrenergic drugs caused approximately the same vasodilation in skin and in muscle; although the duration of the response increased with the dose, the magnitude of the response did not.

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