The effect of urapidil and ramipril on hyperglycemia in streptozotocin diabetic rats

Abstract.

Angiotensin-converting enzyme inhibitors and α₁-adrenoceptor antagonists improve glucose disposal in diabetes mellitus. We compared the effect of the antihypertensive hybrid drug urapidil [α₁-adrenoceptor antagonist serotonin 1A (5-hydroxytryptamine 1A, 5-HT_1A) receptor agonist] on hyperglycemia in streptozotocin diabetic rats with the angiotensin-converting enzyme inhibitor ramipril. 5-HT_1A receptor agonists induce hyperglycemia. This could be an important disadvantage during treatment of diabetes mellitus with urapidil. Diabetes was induced by streptozotocin (70 mg/kg i.p.). Treatment for 7 days (ramipril 10 mg/kg p.o.; urapidil 20 mg/kg p.o.) significantly decreased mean blood glucose values (urapidil: 15.7±0.9 mmol/l, P=0.007; ramipril: 15.0±0.8 mmol/l, P=0.038 vs. diabetic control group: 18.7±1.0 mmol/l). Both drugs reduced significantly blood pressure, urinary glucose, water consumption, and food requirement. Serotonin concentration in the brain (medulla oblongata, pituitary) was not affected. A normalization comparable with healthy control rats was observed only in a diabetic control group with insulin therapy. In conclusion, our results demonstrate that the antihypertensive drug urapidil has no detrimental effect on hyperglycemia compared with the angiotensin-converting enzyme inhibitor ramipril in experimental diabetes mellitus despite its 5-HT_1A receptor agonistic properties.