Alterations in endothelium-dependent hyperpolarization and relaxation in mesenteric arteries from streptozotocin-induced diabetic rats

Abstract

1. The aim of this study was to determine whether endothelium-dependent hyperpolarization and relaxation are altered during experimental diabetes mellitus. Membrane potentials were recorded in mesenteric arteries from rats with streptozotocin-induced diabetes and age-matched controls. 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 in amplitude in diabetic arteries compared with that in controls (maximum -10.4 ± 1.1 vs -17.2 ± 0.8 mV). Furthermore, the hyperpolarizing responses of diabetic arteries were more transient. 2. ACh-induced hyperpolarization observed in control and diabetic arteries remained unaltered even after treatment with 3 x 10-4 M N(G)-nitro-L-arginine (L-NOARG), 10-5 M indomethacin or 60 u ml-1 superoxide dismutase. 3. Endothelium-dependent hyperpolarization with 10-6 M A23187, a calcium ionophore, was also decreased in diabetic arteries compared to controls (-8.3 ± 1.4 vs -18.0 ± 1.9 mV). However, endothelium-independent hyperpolarizing 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 diabetic arteries were almost completely prevented by insulin therapy. Endothelium-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 endothelium-dependent hyperpolarization is reduced by diabetes, and this would, in part, account for the impaired endothelium-dependent relaxations in mesenteric arteries from diabetic rats.