Telmisartan improves vascular function and reduces platelet activation in rats with streptozotocin-induced diabetes mellitus.
Diabetes is associated with vascular dysfunction and platelet activation, both of which may contribute to increased cardiovascular risk. We investigated whether the angiotensin II antagonist telmisartan improves vascular dysfunction and reduces platelet activation in diabetic rats. Therefore, male Wistar rats were injected with streptozotocin (50 mg kg(-1) i.v.) to induce insulin-deficient diabetes. Treatment with telmisartan (10 mg kg(-1)day(-1)) or vehicle was initiated 2 weeks after injection of streptozotocin and continued for 2 weeks. At week 4, platelet activation was assessed in fresh whole blood and vascular function was characterized in isolated aortic segments in organ bath chambers. Diabetic rats displayed severe impairment of endothelium-dependent relaxation induced by acetylcholine as well as endothelium-independent relaxation evoked by a nitric oxide donor, which were improved by treatment with telmisartan. Treatment with telmisartan also improved endogenous platelet vasodilator-stimulated phosphoprotein phosphorylation, which was reduced in platelets from diabetic rats indicating augmented intraluminal vascular nitric oxide bioavailability. Platelets from diabetic rats had increased surface-bound fibrinogen, which was attenuated by telmisartan. Telmisartan normalizes vascular dysfunction and reduces platelet activation in diabetic rats. These effects may contribute to the reduction of cardiovascular events by angiotensin II receptor blockers in diabetic patients.
Medizinische Klinik und Poliklinik I, Universitätsklinikum Würzburg, Julius-Maximilians-Universität Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany. a.schaefer@medizin.uni-wuerzburg.de
Andreas
A
Schäfer
Ulrike
U
Flierl
Christian
C
Vogt
Stefanie
S
Menninger
Piet
P
Tas
Georg
G
Ertl
Johann
J
Bauersachs
D000109:Acetylcholine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004048:Diethylamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077333:Telmisartan; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D000098662:Vasodilator-Stimulated Phosphoprotein
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D015815:Cell Adhesion Molecules; D004048:Diethylamines; D004791:Enzyme Inhibitors; D008840:Microfilament Proteins; D020030:Nitric Oxide Donors; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D000098662:Vasodilator-Stimulated Phosphoprotein; D019335:Nitroarginine; D009569:Nitric Oxide; C087229:diethylamine dinitric oxide adduct; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D000077333:Telmisartan