Effect of three different doses of urapidil on blood glucose concentrations in the streptozotocin diabetic rat

Background and objective: Diabetes mellitus associated with hypertension often causes perioperative complications. The α1-adrenoceptor antagonist/5-hydroxytryptamine-1A receptor agonist urapidil is an approved drug used in hypertension and hypertensive emergencies. 5-Hydroxytryptamine-1A (5-HT1A) receptor agonists impair glucose metabolism. To evaluate a possible dose-dependent hyperglycaemic effect of urapidil due to its 5-HT1A receptor agonistic properties, the effect of three doses of urapidil on hyperglycaemia in the streptozotocin diabetic rat was investigated. Methods: Male Wistar-Kyoto rats were made diabetic by streptozotocin and randomly allocated to the following daily treatments for 7 days (n = 6 each): urapidil 6 mg kg−1, urapidil 20 mg kg−1, urapidil 60 mg kg−1, insulin 4 IU kg−1 subcutaneously. One diabetic group and one non-diabetic healthy group served as controls. Results: Treatment for 7 days with urapidil 20 mg kg−1 and urapidil 60 mg kg−1 reduced mean glucose concentrations significantly (urapidil-20: 15.6 ± 1.1 mmol L−1, P = 0.023; urapidil-60: 15.8 ± 0.8 mmol L−1, P = 0.04) compared with diabetic controls (20.9 ± 0.8 mmol L−1), whereas those after urapidil 6 mg kg−1 were similar to diabetic controls. Insulin treatment normalized blood glucose concentrations. Conclusions: The α1-adrenoceptor antagonist/5-HT1A receptor agonist urapidil has no hyperglycaemic effect on experimental diabetes mellitus, even in high doses, despite its 5-HT1A receptor agonistic properties.