Effect of three different doses of urapidil on blood glucose concentrations in the streptozotocin diabetic rat.
OBJECTIVE
Diabetes mellitus associated with hypertension often causes perioperative complications. The alpha1-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 alpha1-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.
University of Regensburg, Department of Anaesthesiology, Germany. karl-peter.ittner@klinik.uni-regensburg.de
K P
KP
Ittner
M
M
Bucher
M
M
Zimmermann
H E
HE
Grobecker
B K
BK
Krämer
K
K
Taeger
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D005502:Food; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D010879:Piperazines; D013311:Streptozocin; C015568:urapidil