THE EFFECT OF STRESS AND ADRENALECTOMY ON THE RESPONSE TO DICUMAROL IN RATS

Abstract

The prothrombin time was followed in a large number of rats receiving daily doses of dicumarol. Prothrombin times, using the Schwager–Jaques method, were determined on blood samples obtained from the tail vein. It was found that rats, like rabbits, showed a wide variation in their response to dicumarol at dose levels of 10 and 20 mg./kg. body weight per day but, unlike rabbits, they seemed to develop a tolerance to the drug. This began after a peak prothrombin time was reached and occurred later in rats having a higher prothrombin time, or receiving the higher dose of the drug. Stress, in the form of electroshock or sound-induced seizures, increased the variability of the prothrombin time and significantly increased the mean values with 20 mg./kg. dicumarol. These changes persisted in some rats for at least 48 hours. They were prevented by ether anesthesia. Adrenalectomized rats fed dicumarol showed a marked increase in prothrombin time, did not develop tolerance to the drug after a few days, and died of hemorrhage. An analysis of blood samples obtained by cardiac puncture from adrenalectomized, sham-operated, and normal rats fed dicumarol at a dose level of 10 mg./kg. body weight for 5 days showed that values for the Quick one-stage prothrombin times of the adrenalectomized group were elevated significantly above those of the sham-operated and normal groups. No significant differences, however, were noted in the values for the two-stage tests for prothrombin, hematocrit, or plasma dicumarol levels of these animals.