Interaction of Beta-Adrenergic Blocking Agents and Salicylates in the Production of Cardiovascular Malformations

摘要

The possibility that increased beta-adrenergic receptor stimulation might be operative in the production of cardiovascular malformations in rats was studied by exposing pregnant animals to salicylates which produce some cardiovascular defects, and attempting to reduce or inhibit these effects with the beta-receptor blocking agents, propranolol or practolol. Neither propranolol nor practolol alone was toxic to maternal animals or altered any of the reproductive parameters measured. Neither propranolol nor practolol reduced the effect of sodium salicylate on fetal development, including the effect on cardiovascular malformations. In some respects, propranolol in combination with sodium salicylate appeared to enhance the effects of sodium salicylate alone; e.g., an increased number of litters was all resorbed, and an increased incidence of malformed fetuses per litter was observed (excluding those with extra ribs). Thus, the administration of beta-adrenergic blocking agents does not inhibit or reduce the action of salicylates in producing malformations in the rat. This may be due to a lack of effect of salicylates in stimulating beta receptors, or to inadequate placental transfer, metabolism or relatively short half-life of the blocking agents.