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

Angiotensin-converting enzyme inhibitors and alpha(1)-adrenoceptor antagoni sts improve glucose disposal in diabetes mellitus. We compared the effect o f the antihypertensive hybrid drug urapidil [alpha(1)-adrenoceptor antagoni st serotonin 1A (5-hydroxytryptamine 1A, 5-HT1A) receptor agonist] on hyper glycemia in streptozotocin diabetic rats with the angiotensin-converting en zyme inhibitor ramipril. 5-HT1A receptor agonists induce hyper-glycemia. Th is could be an important disadvantage during hypertension occurs in both fo rms of diabetes introduction treatment of diabetes mellitus with urapidil. Diabetes was induced by streptozotocin (70 mg/kg i.p.). Treatment for 7 day s (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 con sumption, and food requirement. Serotonin concentration in the brain (medul la oblongata, pituitary) was not affected. A normalization comparable with healthy control rats was observed only in a diabetic control group with ins ulin therapy. In conclusion, our results demonstrate that the antihypertens ive drug urapidil has no detrimental effect on hyperglycemia compared with the angiotensin-converting enzyme inhibitor ramipil in experimental diabete s mellitus despite its 5-HT1A receptor agonistic properties.