The effect of urapidil and ramipril on hyperglycemia in streptozotocin diabetic rats.
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.
Ittner
K P
KP
Department of Pharmacology, University of Regensburg, Germany. karl-peter.ittner@klinik.uni-regensburg.de
Zimmermann
M
M
Bucher
M
M
Gessele
W
W
Kees
F
F
Krämer
B K
BK
Grobecker
H F
HF
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006029:Glycosuria / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy* / Q000209:etiology; D007328:Insulin / Q000097:blood; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007328:Insulin; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C015568:urapidil; D017257:Ramipril