Lack of endothelium-derived hyperpolarizing factor (EDHF) up-regulation in endothelial dysfunction in aorta in diabetic rats.
Journal Title: Pharmacological Reports - Year 2007, Vol 59, Issue 4
Abstract
It is not known whether the impairment of nitric oxide (NO)-dependent vasodilation of the aorta of diabetic rats is associated with any changes in the endothelial production of vasoactive prostanoids and endothelium-derived hyperpolarizing factor (EDHF). Therefore, we analyzed the contribution of NO, vasoactive prostanoids and EDHF to the decreased endothelium-dependent vasorelaxation in Sprague-Dawley rats at 4 and 8 weeks after diabetes mellitus induced by streptozotocin (STZ). The acetylcholine-induced (Ach) endothelium-dependent relaxation was significantly decreased in the thoracic aorta 8 weeks after the STZ-injection (Ach 10(-6) M: 73.1 +/- 7.4% and 56.7 +/- 7.9% for control and diabetic rats, respectively). The sodium nitroprusside-induced (NaNP) endothelium-independent vasodilation was also impaired in the diabetic rats (8 weeks after STZ) (NaNP 10(-8) M: 74.2 +/- 11.4% and 35.9 +/- 9.4% for control and diabetic rats, respectively). In contrast, the basal NO production, as assessed by the Nomega-nitro-L-arginine methyl ester (L-NAME)-induced vasoconstriction was not modified in diabetes. Moreover, the amount of 6-keto-PGF(1alpha) (stable metabolite of prostacyclin / prostaglandin I(2) / PGI(2) ), 12-L-hydroxy-5,8,10-heptadecatrienoic acid (12-HHT) and thromboxane B(2) (TxB(2) ) (stable metabolite of thromboxane A(2) - TxA(2)) were significantly increased in the 8 weeks diabetic rat aorta. The EDHF-pathway did not change in the aortic endothelium during the development of STZ-induced diabetes. Our results indicate that STZ-induced diabetes mellitus did not modify the basal NO production, but induced the impairment of acetylcholine- and sodium nitroprusside-induced vasodilation in the thoracic aorta. In parallel with the impairment of NO-dependent vasodilation, the basal PGI(2), 12-HHT and TxA(2) synthesis were increased. The EDHF-pathway did not contribute to the endothelium-dependent relaxation either in control or diabetic aorta. The above alterations in the endothelial function may play an important role in the development of endothelial dysfunction and vascular complications of diabetes.
Authors and Affiliations
Gabor Csanyi, Istvan Lepran, Timea Flesch, Gyula Telegdy, Zsofia Mezei
Keywords
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