ADRENERGIC INHIBITORY FUNCTION IN THE RABBIT: EPINEPHRINE REVERSAL AND ISOPROPYLNOREPINEPHRINE VASODEPRESSION

¹ Department of Pharmacology, University of Utah College of Medicine, Salt Lake City. Utah
² Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, Michigan

1. The rabbit possesses adrenergic vascular inhibitory mechanisms.

2. Reversal of the pressor effects of epinephrine can readily be accomplished, provided the following conditions obtain: a) Sufficiently large doses of adrenergic blocking agent must be employed; the rabbit requires much larger doses of such agents than do most other mammals. b) Sufficiently large doses of epinephrine must be employed; small doses in the rabbit do not always exert sufficient vasodilator effect to permit reserval to occur after blockade. c) The blood pressure must be sufficiently high; adequate blood pressure levels seem to be more important in the rabbit than in certain other mammals.

3. Norepinephrine is 50 per cent to 100 per cent as potent as epinephrine in its vasodilator action in the rabbit.

4. Small doses of isopropylnorepinephrine are not consistently depressor and may occasionally be pressor, but larger doses regularly induce a fall in blood pressure. Pressor and diphasic responses can be converted into depressor responses by adrenergic blockage. Therefore, isopropylnorepinephrine pressor responses are the result of vasoconstriction, at least in part.

5. The isopropylnorepinephrine depressor response is a reliable index of vasomotor adrenergic inhibitory function in the rabbit for the following reasons: a) When larger doses of the drug are required for vasodepression, larger doses of epinephrine will likewise be required for reversal after adrenergic blockade. b) After adrenergic blockade the maximum vasodepression in response to isopropylnorepinephrine is the same as that to epinephrine.

6. Reversal of isopropylnorepinephrine depressor responses by ergot alkaloids was not observed in the rabbit under the conditions of this study.

7. Only poor reversals of epinephrine-induced vasoconstriction were observed in the skin of the rabbit when skin temperature was used as an index, but high initial skin temperatures may have masked their appearance.