Abstract
Dichloroisoproterenol (DCI) has been shown previously to prevent both epinephrine-induced augmentation of contractile force and activation of phosphorylase in the dog heart in situ. The present investigation demonstrates that DCI almost completely abolishes the increase in blood glucose and free fatty acids produced by epinephrine, norepinephrine, and isoproterenol in the dog. The hyperlactic acidemic effect of epinephrine is partly blocked. On the other hand DCI does not block epinephrine-induced hyperglycemia in mice.
In contrast to DCI, phenoxybenzamine interferes neither with the hyperglycemia nor the increase in blood lactic acid produced by epinephrine in the dog. Ergotamine antagonizes the hyperglycemia but not the hyperlactic acidemia. Phenoxybenzamine effectively blocks the vasopressor response to norepinephrine and epinephrine, and ergotamine produces maximal reversal of epinephrine. Neither of these drugs in the doses used antagonizes the positive inotropic effect of adrenergic stimuli.
Both DCI and phenoxybenzamine increase blood glucose and lactic acid. High doses of DCI appear to antagonize the hyperglycemic action of low doses. The hyperglycemia and hyperlactic acidemia produced by phenoxybenzamine are antagonized by DCI. DCI also produces a marked and sustained increase in plasma free fatty acids even with doses which do not block this action of norepinephrine.
The relationship of the drug-induced blockade of the metabolic actions of catecholamines with the other actions of adrenergic blocking agents is discussed. Possible mechanisms of actions and classification of adrenotropic receptors subserving the metabolic actions are considered.
Footnotes
- Received April 20, 1961.
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