Ramipril prevents hypersensitivity to phenylephrine in aorta from streptozotocin-induced diabetic rats.
This study investigated the protective effect of the angiotensin converting enzyme inhibitor, ramipril, on endothelium-dependent responses in arteries from control (CON) and streptozotocin-induced (STZ) diabetic rats. Three hypotheses were tested: 1) there is an endothelium-dependent component to the increased alpha-adrenergic responsiveness characteristic of diabetes; 2) endothelium-dependent, acetylcholine-induced relaxation is attenuated in aorta from diabetic rats; and 3) ramipril (3 mg/kg daily in the food, 12-15 weeks) will prevent functional vascular changes in diabetic rats. Vascular function was assessed in aortic rings using standard muscle bath procedures for measurement of isometric force. Sensitivity to phenylephrine was increased in aortic rings from diabetic compared to control values [pD2 values (-log ED50): CON = 6.22 +/- 0.12, STZ = 7.54 +/- 0.11), and removal of the endothelium (-Endo) increased phenylephrine sensitivity (CON-Endo = 7.40 +/- 0.11, STZ-Endo = 8.32 +/- 0.18). The magnitude of the shift in responsiveness following endothelium removal was greatest in control rats. Ramipril treatment (Ram) partially normalized phenylephrine responsiveness in intact (STZ + Ram = 6.55 +/- 0.11) and denuded (STZ-Endo + Ram = 7.75 +/- 0.10) vessels. Vasodilatation to acetylcholine and nitroglycerin was not altered in diabetic rats nor was it affected by ramipril treatment. Diabetes increases contractile sensitivity to phenylephrine but not to vasodilators and chronic ramipril treatment prevents this increase in contractile sensitivity. Ramipril treatment did not alter the hyperglycaemic condition induced by streptozotocin. The changes in phenylephrine sensitivity appear to involve an endothelial and a smooth muscle component.
Department of Physiology, University of Michigan, Ann Arbor.
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P
Murray
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B
Pitt
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RC
Webb
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology*; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D013311:Streptozocin; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D010656:Phenylephrine; D013311:Streptozocin; D017257:Ramipril; D000109:Acetylcholine