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Br J Pharmacol. 1997 Aug;121(7):1383-91.

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

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1
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.

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 +/- 0.8mV). 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 l0(-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.

PMID:
9257918
PMCID:
PMC1564820
DOI:
10.1038/sj.bjp.0701258
[Indexed for MEDLINE]
Free PMC Article
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