Article date: July 1997
By: Mitsuhiro Fukao, Yuichi Hattori, Morio Kanno, Ichiro Sakuma, Akira Kitabatake, in Volume 121, Issue 7, pages 1383-1391
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; 10−8–10−5M) 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.
ACh‐induced hyperpolarization observed in control and diabetic arteries remained unaltered even after treatment with 3×10−4M NG‐nitro‐L‐arginine (L‐NOARG), 10−5M indomethacin or 60 u ml−1 superoxide dismutase.
Endothelium‐dependent hyperpolarization with 10−6M 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 10−6M pinacidil, a potassium channel opener, were similar in control and diabetic arteries (−20.0±1.4 vs −19.2±1.1 mV).
The altered endothelium‐dependent hyperpolarizations in diabetic arteries were almost completely prevented by insulin therapy. Endothelium‐dependent relaxations by ACh in the presence of 10−4ML‐NOARG and 10−5M indomethacin in diabetic arteries were also reduced and more transient compared to controls.
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.
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; 10−8–10−5M) 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.
ACh‐induced hyperpolarization observed in control and diabetic arteries remained unaltered even after treatment with 3×10−4M NG‐nitro‐L‐arginine (L‐NOARG), 10−5M indomethacin or 60 u ml−1 superoxide dismutase.
Endothelium‐dependent hyperpolarization with 10−6M 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 10−6M pinacidil, a potassium channel opener, were similar in control and diabetic arteries (−20.0±1.4 vs −19.2±1.1 mV).
The altered endothelium‐dependent hyperpolarizations in diabetic arteries were almost completely prevented by insulin therapy. Endothelium‐dependent relaxations by ACh in the presence of 10−4ML‐NOARG and 10−5M indomethacin in diabetic arteries were also reduced and more transient compared to controls.
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.
DOI: 10.1038/sj.bjp.0701258
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