Lack of endothelium-derived hyperpolarizing factor (EDHF) up-regulation in endothelial dysfunction in aorta in diabetic rats.
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 N omega-nitro-L-arginine methyl ester (L-NAME)-induced vasoconstriction was not modified in diabetes. Moreover, the amount of 6-keto-PGF(1 alpha) (stable metabolite of prostacyclin / prostaglandin I2 / PGI2 ), 12-L-hydroxy-5,8,10-heptadecatrienoic acid (12-HHT) and thromboxane B2 (TxB2 ) (stable metabolite of thromboxane A2 - TxA2) 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 PGI2, 12-HHT and TxA2 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.
Csanyi
Gabor
G
Department of Pathophysiology, Albert Szent-Gyorgyi Medical and Pharmaceutical Center, University of Szeged, Semmelweis 1, 6725 Szeged, Hungary.
Lepran
Istvan
I
Flesch
Timea
T
Telegdy
Gyula
G
Szabo
Gyula
G
Mezei
Zsofia
Z
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001685:Biological Factors / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D015237:Dinoprost / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D006442:Glycated Hemoglobin / Q000032:analysis; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
D015121:6-Ketoprostaglandin F1 alpha; D000109:Acetylcholine; D001685:Biological Factors; D001786:Blood Glucose; D015237:Dinoprost; D005231:Fatty Acids, Unsaturated; D006442:Glycated Hemoglobin; D007213:Indomethacin; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D009599:Nitroprusside; D010656:Phenylephrine; D013311:Streptozocin; D013928:Thromboxane A2; D013929:Thromboxane B2; C067410:endothelium-dependent hyperpolarization factor; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid