Vascular dysfunction induced by hypochlorite is improved by the selective phosphodiesterase-5-inhibitor vardenafil

• Verfasst von: Radovits, Tamás [VerfasserIn]
• Verfasst von: Arif, Rawa [VerfasserIn]
• Verfasst von: Bömicke, Timo [VerfasserIn]
• Verfasst von: Korkmaz-İçöz, Sevil [VerfasserIn]
• Verfasst von: Barnucz, Enikő [VerfasserIn]
• Verfasst von: Karck, Matthias [VerfasserIn]
• Verfasst von: Merkely, Béla [VerfasserIn]
• Verfasst von: Szabó, Gábor [VerfasserIn]
• Titel: Vascular dysfunction induced by hypochlorite is improved by the selective phosphodiesterase-5-inhibitor vardenafil
• Verf.angabe: Tamás Radovits, Rawa Arif, Timo Bömicke, Sevil Korkmaz, Enikő Barnucz, Matthias Karck, Béla Merkely, Gábor Szabó
• E-Jahr: 2013
• Jahr: 23 April 2013
• Umfang: 10 S.
• Fussnoten: Gesehen am 13.12.2021
• Titel Quelle: Enthalten in: European journal of pharmacology
• Ort Quelle: New York, NY [u.a.] : Elsevier, 1967
• Jahr Quelle: 2013
• Band/Heft Quelle: 710(2013), 1/3 vom: 15. Juni, Seite 110-119
• ISSN Quelle: 1879-0712
• DOI: doi:10.1016/j.ejphar.2013.04.012
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Acetylcholine
• Sach-SW: Animals
• Sach-SW: Aorta, Thoracic
• Sach-SW: Endothelium, Vascular
• Sach-SW: Hypochlorous Acid
• Sach-SW: Imidazoles
• Sach-SW: In Vitro Techniques
• Sach-SW: Male
• Sach-SW: Nitroprusside
• Sach-SW: Oxidants
• Sach-SW: Oxidative Stress
• Sach-SW: Phenylephrine
• Sach-SW: Phosphodiesterase 5 Inhibitors
• Sach-SW: Piperazines
• Sach-SW: Rats
• Sach-SW: Rats, Sprague-Dawley
• Sach-SW: Sulfones
• Sach-SW: Triazines
• Sach-SW: Vardenafil Dihydrochloride
• Sach-SW: Vasoconstrictor Agents
• Sach-SW: Vasodilation
• Sach-SW: Vasodilator Agents
• K10plus-PPN: 1782003231

Abstract

Reactive oxygen species, such as hypochlorite induce oxidative stress, which impairs nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling and leads to vascular dysfunction. It has been proposed, that elevated cGMP-levels may contribute to an effective cytoprotection against oxidative stress. We investigated the effects of vardenafil, a selective inhibitor of the cGMP-degrading phosphodiesterase-5 enzyme on vascular dysfunction induced by hypochlorite. In organ bath experiments for isometric tension, we investigated the endothelium-dependent and endothelium-independent vasorelaxation of isolated rat aortic rings using cumulative concentrations of acetylcholine and sodium nitroprusside (SNP). Vascular dysfunction was induced by exposing rings to hypochlorite (100-400 µM). In the treatment groups, rats were pretreated with vardenafil (30 and 300 µg/kg i.v.). Immunohistochemical analysis was performed for the oxidative stress markers nitrotyrosine, poly(ADP-ribose) and for apoptosis inducing factor (AIF). Exposure to hypochlorite resulted in a marked impairment of acetylcholine-induced endothelium-dependent vasorelaxation of aortic rings. Pretreatment with vardenafil led to improved endothelial function as reflected by the higher maximal vasorelaxation (Rmax) to acetylcholine. Regarding endothelium-independent vasorelaxation, hypochlorite exposure led to a left-shift of SNP concentration-response curves in the vardenafil groups without any alterations of the Rmax. In the hypochlorite groups immunohistochemical analysis showed enhanced poly(ADP-ribose)-formation and nuclear translocation of AIF, which were prevented by vardenafil-pretreatment. Our results support the view that cytoprotective effects of PDE-5-inhibitors on the endothelium may underlie the improved endothelial function, however, a slight sensitisation of vascular smooth muscle to NO was also confirmed. PDE-5-inhibition may represent a potential therapy approach for treating vascular dysfunction induced by oxidative stress.