Lack of endothelium-derived hyperpolarizing factor (EDHF) up-regulation in endothelial dysfunction in aorta in diabetic rats

Gabor Csanyi, Istvan Lepran, Timea Flesch, Gyula Telegdy, Gyula Szabo, Zsofia Mezei

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 Nω-nitro-L-arginine methyt ester (L-NAME)-induced vasoconstriction was not modified in diabetes. Moreover, the amount of 6-keto-PGF1a (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.

Original languageEnglish (US)
Pages (from-to)447-455
Number of pages9
JournalPharmacological Reports
Volume59
Issue number4
StatePublished - Oct 16 2007

Fingerprint

Endothelium
Aorta
Up-Regulation
Vasodilation
Epoprostenol
Nitric Oxide
Streptozocin
Acetylcholine
Experimental Diabetes Mellitus
Nitroprusside
Thoracic Aorta
Prostaglandins
Diabetes Mellitus
Thromboxane B2
Thromboxane A2
NG-Nitroarginine Methyl Ester
Diabetes Complications
Vasoconstriction
Blood Vessels
Sprague Dawley Rats

Keywords

  • Aorta
  • Diabetes
  • EDHF
  • Eicosanoids
  • Nitric oxide
  • Prostaglandins

ASJC Scopus subject areas

  • Pharmacology

Cite this

Lack of endothelium-derived hyperpolarizing factor (EDHF) up-regulation in endothelial dysfunction in aorta in diabetic rats. / Csanyi, Gabor; Lepran, Istvan; Flesch, Timea; Telegdy, Gyula; Szabo, Gyula; Mezei, Zsofia.

In: Pharmacological Reports, Vol. 59, No. 4, 16.10.2007, p. 447-455.

Research output: Contribution to journalArticle

Csanyi, Gabor ; Lepran, Istvan ; Flesch, Timea ; Telegdy, Gyula ; Szabo, Gyula ; Mezei, Zsofia. / Lack of endothelium-derived hyperpolarizing factor (EDHF) up-regulation in endothelial dysfunction in aorta in diabetic rats. In: Pharmacological Reports. 2007 ; Vol. 59, No. 4. pp. 447-455.
@article{3cdc4c41971c4e3dbae1231da61af73a,
title = "Lack of endothelium-derived hyperpolarizing factor (EDHF) up-regulation in endothelial dysfunction in aorta in diabetic rats",
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 Nω-nitro-L-arginine methyt ester (L-NAME)-induced vasoconstriction was not modified in diabetes. Moreover, the amount of 6-keto-PGF1a (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.",
keywords = "Aorta, Diabetes, EDHF, Eicosanoids, Nitric oxide, Prostaglandins",
author = "Gabor Csanyi and Istvan Lepran and Timea Flesch and Gyula Telegdy and Gyula Szabo and Zsofia Mezei",
year = "2007",
month = "10",
day = "16",
language = "English (US)",
volume = "59",
pages = "447--455",
journal = "Pharmacological Reports",
issn = "1734-1140",
publisher = "Polish Academy of Sciences Publishing House",
number = "4",

}

TY - JOUR

T1 - Lack of endothelium-derived hyperpolarizing factor (EDHF) up-regulation in endothelial dysfunction in aorta in diabetic rats

AU - Csanyi, Gabor

AU - Lepran, Istvan

AU - Flesch, Timea

AU - Telegdy, Gyula

AU - Szabo, Gyula

AU - Mezei, Zsofia

PY - 2007/10/16

Y1 - 2007/10/16

N2 - 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 Nω-nitro-L-arginine methyt ester (L-NAME)-induced vasoconstriction was not modified in diabetes. Moreover, the amount of 6-keto-PGF1a (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.

AB - 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 Nω-nitro-L-arginine methyt ester (L-NAME)-induced vasoconstriction was not modified in diabetes. Moreover, the amount of 6-keto-PGF1a (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.

KW - Aorta

KW - Diabetes

KW - EDHF

KW - Eicosanoids

KW - Nitric oxide

KW - Prostaglandins

UR - http://www.scopus.com/inward/record.url?scp=35048876130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35048876130&partnerID=8YFLogxK

M3 - Article

C2 - 17901574

AN - SCOPUS:35048876130

VL - 59

SP - 447

EP - 455

JO - Pharmacological Reports

JF - Pharmacological Reports

SN - 1734-1140

IS - 4

ER -