RESISTANCE TO THE EFFECT OF CARBACHOL ON THE CARDIOVASCULAR SYSTEM AND ON THE ISOLATED ILEUM OF RATS AFTER SUBACUTE ADMINISTRATION OF AN ORGANOPHOSPHORUS CHOLINESTERASE INHIBITOR

¹ Department of Pharmacology, Medical College of Virginia, Richmond, Virginia

The subacute administration of Di-Syston to rats was accompanied by an increased resistance to the cardiovascular effect of carbachol and to the effect of carbachol on the isolated ileum. Maximal resistance to the negative chronotropic and hypotensive actions of carbachol was observed in Di-Syston-treated rats after 10 days of treatment. When the dose of carbachol was extended to 300 µg/kg, Di-Syston-treated rats exhibited only a slight transient depressor response which was then followed by a pressor response. In control rats, however, carbachol, in doses of 30 µg/kg and higher, consistently produced cardiac arrest and a marked drop in blood pressure. In the isolated ileum, maximal resistance to the effect of carbachol was observed after 3 days of treatment with Di-Syston. At the same time the cholinesterase activity of the ileum was reduced to 50% of control values. Treatment of the rats for longer periods of time did not produce any greater depression of cholinesterase or any significant increase in resistance to carbachol.