title: Effects of telmisartan or amlodipine monotherapy versus telmisartan/amlodipine combination therapy on vascular dysfunction and oxidative stress in diabetic rats.
abstract: Our previous studies identified potent antioxidant effects and improvement of vascular function by telmisartan therapy in experimental diabetes and nitrate tolerance. The present study compared the beneficial effects of single telmisartan or amlodipine versus telmisartan/amlodipine combination therapy (T+A) in streptozotocin (STZ)-induced type 1 diabetic rats. Male Wistar rats were injected once with STZ (60 mg/kg, i.v.) and 1 week later the drugs (telmisartan, amlodipine, or T+A) were administrated orally by a special diet (2.5-5 mg kg(-1) day(-1)) for another 7 weeks. We only observed a marginal beneficial on-top effect of T+A therapy over the single drug regimen that was most evident in the improvement of endothelial function (acetylcholine response) and less pronounced in the reduction of whole blood, vascular and cardiac oxidative stress (blood leukocyte oxidative burst, aortic dihydroethidine and 3-nitrotyrosine staining, as well as cardiac NADPH oxidase activity and uncoupling of endothelial nitric oxide synthase) in diabetic rats. These effects on oxidative stress parameters were paralleled by those on the expression pattern of NADPH oxidase and nitric oxide synthase isoforms. In addition, development of mild hypotension in the T+A-treated rats was observed. Reasons for this moderate synergistic effect of T+A therapy may be related to the potent beneficial effects of telmisartan alone and the fact that amlodipine and telmisartan share similar pathways to improve endothelial function. Moreover, hypotension in the T+A-treated rats could partially antagonize the beneficial additive effects by counter-regulatory mechanisms (e.g., activation of the renin-angiotensin-aldosterone system).
authors: 2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors: Hanke
authors: H
authors: Mollnau
authors: Matthias
authors: M
authors: Oelze
authors: Elena
authors: E
authors: Zinßius
authors: Michael
authors: M
authors: Hausding
authors: Zhixiong
authors: Z
authors: Wu
authors: Maike
authors: M
authors: Knorr
authors: Jasmin
authors: J
authors: Ghaemi Kerahrodi
authors: Swenja
authors: S
authors: Kröller-Schön
authors: Thomas
authors: T
authors: Jansen
authors: Christine
authors: C
authors: Teutsch
authors: Carolyn
authors: C
authors: Foster
authors: Huige
authors: H
authors: Li
authors: Philip
authors: P
authors: Wenzel
authors: Eberhard
authors: E
authors: Schulz
authors: Thomas
authors: T
authors: Münzel
authors: Andreas
authors: A
authors: Daiber
mesh_terms: D017311:Amlodipine / Q000008:administration & dosage*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage*; D001565:Benzoates / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000077333:Telmisartan; D016896:Treatment Outcome
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D004338:Drug Combinations; C548840:telmisartan amlodipine combination; D017311:Amlodipine; D000077333:Telmisartan