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Improvement of vascular function by acute and chronic treatment with the PDE-5 inhibitor sildenafil in experimental diabetes mellitus

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Improvement of vascular function by acute and chronic treatment with the PDE-5 inhibitor sildenafil in experimental diabetes mellitus. / Schäfer, A; Fraccarollo, D; Pförtsch, S; Flierl, U; Vogt, C; Pfrang, J; Kobsar, A; Renné, T; Eigenthaler, M; Ertl, G; Bauersachs, J.

in: BRIT J PHARMACOL, Jahrgang 153, Nr. 5, 01.03.2008, S. 886-93.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Schäfer, A, Fraccarollo, D, Pförtsch, S, Flierl, U, Vogt, C, Pfrang, J, Kobsar, A, Renné, T, Eigenthaler, M, Ertl, G & Bauersachs, J 2008, 'Improvement of vascular function by acute and chronic treatment with the PDE-5 inhibitor sildenafil in experimental diabetes mellitus', BRIT J PHARMACOL, Jg. 153, Nr. 5, S. 886-93. https://doi.org/10.1038/sj.bjp.0707459

APA

Schäfer, A., Fraccarollo, D., Pförtsch, S., Flierl, U., Vogt, C., Pfrang, J., Kobsar, A., Renné, T., Eigenthaler, M., Ertl, G., & Bauersachs, J. (2008). Improvement of vascular function by acute and chronic treatment with the PDE-5 inhibitor sildenafil in experimental diabetes mellitus. BRIT J PHARMACOL, 153(5), 886-93. https://doi.org/10.1038/sj.bjp.0707459

Vancouver

Schäfer A, Fraccarollo D, Pförtsch S, Flierl U, Vogt C, Pfrang J et al. Improvement of vascular function by acute and chronic treatment with the PDE-5 inhibitor sildenafil in experimental diabetes mellitus. BRIT J PHARMACOL. 2008 Mär 1;153(5):886-93. https://doi.org/10.1038/sj.bjp.0707459

Bibtex

@article{fd85429de0394b7ba8600ac132246dfd,
title = "Improvement of vascular function by acute and chronic treatment with the PDE-5 inhibitor sildenafil in experimental diabetes mellitus",
abstract = "BACKGROUND AND PURPOSE: Diabetes-associated vascular dysfunction contributes to increased cardiovascular risk. We investigated whether the phosphodiesterase-5 inhibitor sildenafil would improve vascular function in diabetic rats.EXPERIMENTAL APPROACH: Male Wistar rats were injected with streptozotocin (50 mg kg(-1), i.v.) to induce insulin-deficient diabetes. Direct effects of sildenafil as well as modification of endothelium-dependent and -independent vasorelaxation were investigated in vitro. The effects of acute and chronic (2 week) treatment in vivo of sildenafil on vascular function were also characterized in isolated aortic segments in organ bath chambers 4 weeks after diabetes induction.KEY RESULTS: Sildenafil induced a concentration-dependent vasorelaxation, which was attenuated by the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine. Acetylcholine-induced endothelium-dependent as well as endothelium-independent relaxation induced by the NO donor, DEA-NONOate, was significantly reduced in aortae from diabetic rats. Incubation with sildenafil in vitro normalized both endothelium-dependent and -independent relaxation in aortae from diabetic rats. Acute as well as chronic in vivo treatment with sildenafil resulted in enhanced endothelium-dependent and -independent vasorelaxation. Superoxide formation was increased in diabetes, associated with enhanced membrane expression of the NAD(P)H oxidase subunit gp91(phox) and Rac, which were both reduced by chronic treatment with sildenafil.CONCLUSIONS AND IMPLICATIONS: We demonstrate that sildenafil treatment rapidly and chronically improves vascular relaxation in diabetic rats. Treatment with sildenafil might provide a similarly beneficial effect in diabetic patients.",
keywords = "Acetylcholine, Animals, Aorta, Thoracic, Diabetes Mellitus, Experimental, Dose-Response Relationship, Drug, Drug Administration Schedule, Endothelium, Vascular, Male, Nitric Oxide Synthase, Oxidative Stress, Phosphodiesterase Inhibitors, Piperazines, Purines, Rats, Rats, Wistar, Streptozocin, Sulfones, Superoxides, Vasodilation",
author = "A Sch{\"a}fer and D Fraccarollo and S Pf{\"o}rtsch and U Flierl and C Vogt and J Pfrang and A Kobsar and T Renn{\'e} and M Eigenthaler and G Ertl and J Bauersachs",
year = "2008",
month = mar,
day = "1",
doi = "10.1038/sj.bjp.0707459",
language = "English",
volume = "153",
pages = "886--93",
journal = "BRIT J PHARMACOL",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

TY - JOUR

T1 - Improvement of vascular function by acute and chronic treatment with the PDE-5 inhibitor sildenafil in experimental diabetes mellitus

AU - Schäfer, A

AU - Fraccarollo, D

AU - Pförtsch, S

AU - Flierl, U

AU - Vogt, C

AU - Pfrang, J

AU - Kobsar, A

AU - Renné, T

AU - Eigenthaler, M

AU - Ertl, G

AU - Bauersachs, J

PY - 2008/3/1

Y1 - 2008/3/1

N2 - BACKGROUND AND PURPOSE: Diabetes-associated vascular dysfunction contributes to increased cardiovascular risk. We investigated whether the phosphodiesterase-5 inhibitor sildenafil would improve vascular function in diabetic rats.EXPERIMENTAL APPROACH: Male Wistar rats were injected with streptozotocin (50 mg kg(-1), i.v.) to induce insulin-deficient diabetes. Direct effects of sildenafil as well as modification of endothelium-dependent and -independent vasorelaxation were investigated in vitro. The effects of acute and chronic (2 week) treatment in vivo of sildenafil on vascular function were also characterized in isolated aortic segments in organ bath chambers 4 weeks after diabetes induction.KEY RESULTS: Sildenafil induced a concentration-dependent vasorelaxation, which was attenuated by the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine. Acetylcholine-induced endothelium-dependent as well as endothelium-independent relaxation induced by the NO donor, DEA-NONOate, was significantly reduced in aortae from diabetic rats. Incubation with sildenafil in vitro normalized both endothelium-dependent and -independent relaxation in aortae from diabetic rats. Acute as well as chronic in vivo treatment with sildenafil resulted in enhanced endothelium-dependent and -independent vasorelaxation. Superoxide formation was increased in diabetes, associated with enhanced membrane expression of the NAD(P)H oxidase subunit gp91(phox) and Rac, which were both reduced by chronic treatment with sildenafil.CONCLUSIONS AND IMPLICATIONS: We demonstrate that sildenafil treatment rapidly and chronically improves vascular relaxation in diabetic rats. Treatment with sildenafil might provide a similarly beneficial effect in diabetic patients.

AB - BACKGROUND AND PURPOSE: Diabetes-associated vascular dysfunction contributes to increased cardiovascular risk. We investigated whether the phosphodiesterase-5 inhibitor sildenafil would improve vascular function in diabetic rats.EXPERIMENTAL APPROACH: Male Wistar rats were injected with streptozotocin (50 mg kg(-1), i.v.) to induce insulin-deficient diabetes. Direct effects of sildenafil as well as modification of endothelium-dependent and -independent vasorelaxation were investigated in vitro. The effects of acute and chronic (2 week) treatment in vivo of sildenafil on vascular function were also characterized in isolated aortic segments in organ bath chambers 4 weeks after diabetes induction.KEY RESULTS: Sildenafil induced a concentration-dependent vasorelaxation, which was attenuated by the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine. Acetylcholine-induced endothelium-dependent as well as endothelium-independent relaxation induced by the NO donor, DEA-NONOate, was significantly reduced in aortae from diabetic rats. Incubation with sildenafil in vitro normalized both endothelium-dependent and -independent relaxation in aortae from diabetic rats. Acute as well as chronic in vivo treatment with sildenafil resulted in enhanced endothelium-dependent and -independent vasorelaxation. Superoxide formation was increased in diabetes, associated with enhanced membrane expression of the NAD(P)H oxidase subunit gp91(phox) and Rac, which were both reduced by chronic treatment with sildenafil.CONCLUSIONS AND IMPLICATIONS: We demonstrate that sildenafil treatment rapidly and chronically improves vascular relaxation in diabetic rats. Treatment with sildenafil might provide a similarly beneficial effect in diabetic patients.

KW - Acetylcholine

KW - Animals

KW - Aorta, Thoracic

KW - Diabetes Mellitus, Experimental

KW - Dose-Response Relationship, Drug

KW - Drug Administration Schedule

KW - Endothelium, Vascular

KW - Male

KW - Nitric Oxide Synthase

KW - Oxidative Stress

KW - Phosphodiesterase Inhibitors

KW - Piperazines

KW - Purines

KW - Rats

KW - Rats, Wistar

KW - Streptozocin

KW - Sulfones

KW - Superoxides

KW - Vasodilation

U2 - 10.1038/sj.bjp.0707459

DO - 10.1038/sj.bjp.0707459

M3 - SCORING: Journal article

C2 - 17891166

VL - 153

SP - 886

EP - 893

JO - BRIT J PHARMACOL

JF - BRIT J PHARMACOL

SN - 0007-1188

IS - 5

ER -