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

T. Radovits, Rawa Arif, Timo Bömicke, Sevil Korkmaz, Eniko Barnucz, Matthias Karck, B. Merkely, G. Szabó

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)110-119
Number of pages10
JournalEuropean Journal of Pharmacology
Volume710
Issue number1-3
DOIs
Publication statusPublished - Jun 15 2013

Fingerprint

Hypochlorous Acid
Phosphodiesterase 5 Inhibitors
Blood Vessels
Endothelium
Vasodilation
Cyclic GMP
Oxidative Stress
Apoptosis Inducing Factor
Poly Adenosine Diphosphate Ribose
Acetylcholine
Nitroprusside
Nitric Oxide
Type 5 Cyclic Nucleotide Phosphodiesterases
Cytoprotection
Baths
Vascular Smooth Muscle
Vardenafil Dihydrochloride
Reactive Oxygen Species
Enzymes
Therapeutics

Keywords

  • Endothelial dysfunction
  • Hypochlorite
  • Oxidative stress
  • Phosphodiesterase-5
  • Vardenafil

ASJC Scopus subject areas

  • Pharmacology

Cite this

Vascular dysfunction induced by hypochlorite is improved by the selective phosphodiesterase-5-inhibitor vardenafil. / Radovits, T.; Arif, Rawa; Bömicke, Timo; Korkmaz, Sevil; Barnucz, Eniko; Karck, Matthias; Merkely, B.; Szabó, G.

In: European Journal of Pharmacology, Vol. 710, No. 1-3, 15.06.2013, p. 110-119.

Research output: Contribution to journalArticle

Radovits, T. ; Arif, Rawa ; Bömicke, Timo ; Korkmaz, Sevil ; Barnucz, Eniko ; Karck, Matthias ; Merkely, B. ; Szabó, G. / Vascular dysfunction induced by hypochlorite is improved by the selective phosphodiesterase-5-inhibitor vardenafil. In: European Journal of Pharmacology. 2013 ; Vol. 710, No. 1-3. pp. 110-119.
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