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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 361; no. 1; pp. 92 - 97
• Main Authors: Ittner, K P, Zimmermann, M, Bucher, M, Gessele, W, Kees, F, Krämer, B K, Grobecker, H F
• Format: Journal Article
• Language: English
• Published: Germany 01-01-2000
• Subjects: Adrenergic alpha-Antagonists - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Blood Glucose - metabolism; Blood Pressure - drug effects; Body Weight - drug effects; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - metabolism; Drinking - drug effects; Eating - drug effects; Glycosuria - metabolism; Hyperglycemia - drug therapy; Hyperglycemia - etiology; Insulin - blood; Male; Medulla Oblongata - drug effects; Medulla Oblongata - metabolism; Piperazines - pharmacology; Pituitary Gland - drug effects; Pituitary Gland - metabolism; Ramipril - pharmacology; Rats; Rats, Inbred WKY; Serotonin - metabolism; Serotonin Receptor Agonists - pharmacology
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s002109900157

Angiotensin-converting enzyme inhibitors and alpha1-adrenoceptor antagonists improve glucose disposal in diabetes mellitus. We compared the effect of the antihypertensive hybrid drug urapidil [alpha1-adrenoceptor antagonist serotonin 1A (5-hydroxytryptamine 1A, 5-HT1A) receptor agonist] on hyperglycemia in streptozotocin diabetic rats with the angiotensin-converting enzyme inhibitor ramipril. 5-HT1A 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-HT1A receptor agonistic properties.