ALTERATIONS IN ENDOTHELIUM-DEPENDENT HYPERPOLARIZATION AND RELAXATIONIN MESENTERIC-ARTERIES FROM STREPTOZOTOCIN-INDUCED DIABETIC RATS

1 The aim of this study was to determine whether endothelium-dependent hyperpolarization and relaxation are altered during experimental diab etes mellitus. Membrane potentials were recorded in mesenteric arterie s from rats with streptozotocin-induced diabetes and age-matched contr ols. The resting membrane potentials were not significantly different between control and diabetic mesenteric arteries (-55.3+/-0.5 vs -55.6 +/-0.4 mV). However, endothelium-dependent hyperpolarization produced by acetylcholine (ACh; 10(-8)-10(-5) M) was significantly diminished i n amplitude in diabetic arteries compared with that in controls (maxim um -10.4+/-1.1 vs -17.2+/-0.8 mV). Furthermore, the hyperpolarizing re sponses of diabetic arteries were more transient. 2 ACh-induced hyperp olarization observed in control and diabetic arteries remained unalter ed even after treatment with 3 x 10(-4) M N-G-nitro-L-arginine (L-NOAR G), 10(-5) M indomethacin or 60 u ml(-1) superoxide dismutase. 3 Endot helium-dependent hyperpolarization with 10(-6) M A23187, a calcium ion ophore, was also decreased in diabetic arteries compared to controls ( -8.3+/-1.4 vs -18.0+/-1.9 mV). However, endothelium-independent hyperp olarizing responses to 10(-6) M pinacidil, a potassium channel opener, were similar in control and diabetic arteries (-20.0+/-1.4 vs -19.2+/ -1.1 mV). 4 The altered endothelium-dependent hyperpolarizations in di abetic arteries were almost completely prevented by insulin therapy. E ndothelium-dependent relaxations by ACh in the presence of 10(-4) M L- NOARG and 10(-5) M indomethacin in diabetic arteries were also reduced and more transient compared to controls. 5 These data indicate that e ndothelium-dependent hyperpolarization is reduced by diabetes, and thi s would, in part, account for the impaired endothelium-dependent relax ations in mesenteric arteries from diabetic rats.