IMPAIRED CONTRACTION AND ENDOTHELIUM-DEPENDENT RELAXATION IN ISOLATEDRESISTANCE VESSELS FROM PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

1. An increase in capillary blood flow and pressure has been implicate d in the pathogenesis of diabetic microangiopathy. Abnormal vascular r eactivity of the resistance vasculature may play a contributory role b y permitting alterations in regional haemodynamics. 2. We have studied the contractile behavior of isolated resistance arteries from normote nsive patients with insulin-dependent diabetes mellitus and non-diabet ic matched control subjects. Contractile responses to potassium (123 m mol/l), noradrenaline (10(-8) to 3 x 10(-5) mol/l) and angiotensin II (10(-11) to 3 x 10(-8) mol/l) were recorded. Relaxation studies were p erformed in maximally contracted vessels using acetylcholine(10(-8) to 10(-5) mol/l) and bradykinin(10(-9) to 10(-6) mol/l) (endothelium-dep endent) and sodium nitroprusside (10(-9) to 10(-5) mol/l) (endothelium -independent). 3. The maximal contractile responses to potassium (P<0. 05), noradrenaline (P<0.01) and angiotensin II (P<0.01) were depressed in diabetic patients. Relaxation to acetylcholine was impaired (P< 0. 05), but was normal with bradykinin and sodium nitroprusside. 4. These results suggest that there may be a defect in the endothelial cell ac etylcholine receptor excitation-coupling in diabetes mellitus rather t han a decreased ability to synthesize and release endothelium-derived relaxing factor. Impaired contraction and endothelium-dependent relaxa tion of resistance arteries in diabetic patients may contribute to the development of diabetic microangiopathy by causing an increase in tis sue blood flow, a rise in capillary pressure and, as a result, an incr ease in vascular permeability.