Vascular dysfunction induced by hypochlorite is improved by the selective phosphodiesterase-5-inhibitor vardenafil / Tamás Radovits, Rawa Arif, Timo Bömicke, Sevil Korkmaz, Enikő Barnucz, Matthias Karck, Béla Merkely, Gábor Szabó
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..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
23 April 2013 2013 |
|---|---|
| Erschienen: |
23 April 2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:710 |
|---|---|
| Enthalten in: |
European journal of pharmacology - 710(2013), 1/3 vom: 15. Juni, Seite 110-119 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Radovits, Tamás [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Gesehen am 13.12.2021 |
|---|
| Umfang: |
10 |
|---|
| doi: |
10.1016/j.ejphar.2013.04.012 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
1782003231 |
|---|
| LEADER | 01000caa a2200265 4500 | ||
|---|---|---|---|
| 001 | 1782003231 | ||
| 003 | DE-627 | ||
| 005 | 20230426163127.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 211213s2013 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejphar.2013.04.012 |2 doi | |
| 035 | |a (DE-627)1782003231 | ||
| 035 | |a (DE-599)KXP1782003231 | ||
| 035 | |a (OCoLC)1341436225 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 100 | 1 | |a Radovits, Tamás |e verfasserin |0 (DE-588)1081943203 |0 (DE-627)846898101 |0 (DE-576)454965869 |4 aut | |
| 245 | 1 | 0 | |a Vascular dysfunction induced by hypochlorite is improved by the selective phosphodiesterase-5-inhibitor vardenafil |c Tamás Radovits, Rawa Arif, Timo Bömicke, Sevil Korkmaz, Enikő Barnucz, Matthias Karck, Béla Merkely, Gábor Szabó |
| 264 | 1 | |c 23 April 2013 | |
| 300 | |a 10 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 13.12.2021 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a Acetylcholine | |
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Aorta, Thoracic | |
| 650 | 4 | |a Endothelium, Vascular | |
| 650 | 4 | |a Hypochlorous Acid | |
| 650 | 4 | |a Imidazoles | |
| 650 | 4 | |a In Vitro Techniques | |
| 650 | 4 | |a Male | |
| 650 | 4 | |a Nitroprusside | |
| 650 | 4 | |a Oxidants | |
| 650 | 4 | |a Oxidative Stress | |
| 650 | 4 | |a Phenylephrine | |
| 650 | 4 | |a Phosphodiesterase 5 Inhibitors | |
| 650 | 4 | |a Piperazines | |
| 650 | 4 | |a Rats | |
| 650 | 4 | |a Rats, Sprague-Dawley | |
| 650 | 4 | |a Sulfones | |
| 650 | 4 | |a Triazines | |
| 650 | 4 | |a Vardenafil Dihydrochloride | |
| 650 | 4 | |a Vasoconstrictor Agents | |
| 650 | 4 | |a Vasodilation | |
| 650 | 4 | |a Vasodilator Agents | |
| 700 | 1 | |a Arif, Rawa |d 1984- |e verfasserin |0 (DE-588)1023582775 |0 (DE-627)718414071 |0 (DE-576)367034530 |4 aut | |
| 700 | 1 | |a Bömicke, Timo |e verfasserin |4 aut | |
| 700 | 1 | |a Korkmaz-İçöz, Sevil |e verfasserin |0 (DE-588)1062748697 |0 (DE-627)806830336 |0 (DE-576)420147845 |4 aut | |
| 700 | 1 | |a Barnucz, Enikő |e verfasserin |4 aut | |
| 700 | 1 | |a Karck, Matthias |d 1961- |e verfasserin |0 (DE-588)130833525 |0 (DE-627)505909340 |0 (DE-576)298366169 |4 aut | |
| 700 | 1 | |a Merkely, Béla |e verfasserin |4 aut | |
| 700 | 1 | |a Szabó, Gábor |d 1969- |e verfasserin |0 (DE-588)1022955152 |0 (DE-627)717338681 |0 (DE-576)366215485 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of pharmacology |d New York, NY [u.a.] : Elsevier, 1967 |g 710(2013), 1/3 vom: 15. Juni, Seite 110-119 |h Online-Ressource |w (DE-627)300897340 |w (DE-600)1483526-5 |w (DE-576)081952627 |x 1879-0712 |7 nnns |
| 773 | 1 | 8 | |g volume:710 |g year:2013 |g number:1/3 |g day:15 |g month:06 |g pages:110-119 |g extent:10 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.ejphar.2013.04.012 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S0014299913003051?via%3Dihub |x Verlag |z lizenzpflichtig |3 Volltext |
| 912 | |a GBV_USEFLAG_U | ||
| 912 | |a GBV_ILN_2013 | ||
| 912 | |a ISIL_DE-16-250 | ||
| 912 | |a SYSFLAG_1 | ||
| 912 | |a GBV_KXP | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_31 | ||
| 912 | |a GBV_ILN_65 | ||
| 912 | |a GBV_ILN_702 | ||
| 912 | |a GBV_ILN_2003 | ||
| 912 | |a GBV_ILN_2011 | ||
| 912 | |a GBV_ILN_2025 | ||
| 912 | |a GBV_ILN_2111 | ||
| 912 | |a GBV_ILN_2190 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4035 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4313 | ||
| 936 | u | w | |d 710 |j 2013 |e 1/3 |b 15 |c 6 |h 110-119 |g 10 |
| 951 | |a AR | ||
| 952 | |d 710 |j 2013 |e 1/3 |b 15 |c 6 |h 110-119 |g 10 | ||
| 980 | |2 2013 |1 01 |x DE-16-250 |b 401947365X |c 00 |f --%%-- |d --%%-- |e --%%-- |j --%%-- |y l01 |z 13-12-21 | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 00 |s s |a hd2013 | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 01 |s s |0 (DE-627)1410508463 |a wissenschaftlicher Artikel (Zeitschrift) | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 02 |s s |a per_8 | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 03 |s s |a s_10 | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 04 |s p |0 (DE-627)1450618936 |a Arif, Rawa | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 04 |s k |0 (DE-627)1416740848 |a Chirurgische Universitätsklinik | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 04 |s s |0 (DE-627)1410501914 |a Verfasser | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 04 |s s |a pos_2 | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 05 |s p |0 (DE-627)1490149120 |a Korkmaz-İçöz, Sevil | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 05 |s k |0 (DE-627)1416740848 |a Chirurgische Universitätsklinik | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 05 |s s |0 (DE-627)1410501914 |a Verfasser | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 05 |s s |a pos_4 | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 06 |s p |0 (DE-627)1449896383 |a Karck, Matthias | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 06 |s k |0 (DE-627)1416740848 |a Chirurgische Universitätsklinik | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 06 |s s |0 (DE-627)1410501914 |a Verfasser | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 06 |s s |a pos_6 | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 07 |s p |0 (DE-627)1436216044 |a Szabó, Gábor | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 07 |s k |0 (DE-627)1416740848 |a Chirurgische Universitätsklinik | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 07 |s k |0 (DE-627)1416466967 |a Medizinische Fakultät Heidelberg | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 07 |s s |0 (DE-627)1410501914 |a Verfasser | ||
| 982 | |2 2013 |1 01 |x DE-16-250 |8 07 |s s |a pos_8 | ||