Histamine antagonists in the treatment of shock hyperglycemia in the rat

The present study was undertaken to determine the effect of exogenous histamine and histamine blockers on blood glucose and hepatic glycogen in the rat. Forty-one nonfasted male Sprague-Dawley rats that had been anesthetized with intraperitoneal injections of urethane were injected intravenously (femoral) with histamine (10 mg/kg) five minutes after pretreatment with Ringer's solution (control), diphenhydramine (1 mg/kg) (H-1 blocker); metiamide (1 mg/kg) (H-2 blocker); or a combination of these blockers. Mean arterial pressure (carotid), blood glucose, and hepatic glycogen were measured. Within 30 minutes, histamine evoked a significant increase in blood glucose, and a decrease in hepatic glycogen, and a reduction in blood pressure. However, rats treated with the H-2 blocker metiamide or with a combination of H-1 and H-2 blockers did not show as significant a hypotensive response as rats treated with the H-1 blocker diphenhydramine alone. The hyperglycemic-glycogenolytic response to histamine was modified by diphenhydramine as well as by a combination of blockers, but not by metiamide alone. These results suggest that a) the hypotension did not initiate the hyperglycemic and glycogenolytic response; b) the H-2 blocker metiamide has little effect on the hyperglycemic response to exogenous histamine; and c) the H-1 blocker diphenhydramine may have antihyperglycemic properties.