RAMIPRIL PREVENTS HYPERSENSITIVITY TO PHENYLEPHRINE IN AORTA FROM STREPTOZOTOCIN-INDUCED DIABETIC RATS

This study investigated the protective effect of the angiotensin conve rting enzyme inhibitor, ramipril, on endothelium-dependent responses i n arteries from control (CON) and strep tozotocin-induced (STZ) diabet ic rats. Three hypotheses were tested: 1) there is an endothelium-depe ndent component to the increased alpha-adrenergic responsiveness chara cteristic 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 vasc ular changes in diabetic rats. Vascular function was assessed in aorti c rings using standard muscle bath procedures for measurement of isome tric force. Sensitivity to phenylephrine was increased in aortic rings from diabetic compared to control values [pD(2) values (-log ED(50)): CON = 6.22 +/- 0.12, STZ = 7.54 +/- 0.11), and removal of the endothe lium (-Endo) increased phenylephrine sensitivity (CON-Endo = 7.40 +/- 0.11, STZ-Endo = 8.32 +/- 0.18). The magnitude of the shift in respons iveness following endothelium removal was greatest in control rats. Ra mipril treatment (Ram) partially normalized phenylephrine responsivene ss in intact (STZ + Ram = 6.55 +/- 0.11) and denuded (STZ-Endo + Ram = 7.75 +/- 0.10) vessels. Vasodilatation to acetylcholine and nitroglyc erin 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 smoo th muscle component.