Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation
Introduction. The aim of this study was to investigate whether activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) contributes to the development of aldosterone-induced endothelial dysfunction and treatment with the potent PARP inhibitor 1,5-isoquinolinediol (3 mg/kg/day, i.p.) could...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publications
2009-09-01
|
| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/1470320309343655 |
| _version_ | 1797284144279977984 |
|---|---|
| author | Arda Tasatargil Merih Tekcan Ciler Celik-Ozenci Nazli Ece Gungor Bedriniam Dalkiran |
| author_facet | Arda Tasatargil Merih Tekcan Ciler Celik-Ozenci Nazli Ece Gungor Bedriniam Dalkiran |
| author_sort | Arda Tasatargil |
| collection | DOAJ |
| description | Introduction. The aim of this study was to investigate whether activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) contributes to the development of aldosterone-induced endothelial dysfunction and treatment with the potent PARP inhibitor 1,5-isoquinolinediol (3 mg/kg/day, i.p.) could prevent endothelial dysfunction caused by aldosterone. Methods. Infusion of subpressor doses of aldosterone with subcutaneously implanted mini-osmotic pumps (0.05 mg/kg/day) to rats for 21 days induced the development of endothelial dysfunction. In order to evaluate endothelial function, isometric tension studies were performed in response to acetylcholine and sodium nitroprusside.Additionally, PAR (the end product of activated PARP) and PARP-1 expressions in the endothelium of thoracic aortas were evaluated by immunohistochemistry. Results. There was a significant loss of endothelium-dependent vasodilatation in response to acetylcholine in aldosterone-infused rats. In animals treated with 1,5-isoquinolinediol, the effect of aldosterone on vascular responsiveness was less than the untreated groups. Immunohistochemical studies demonstrated that aldosterone administration increased PAR and PARP-1 expressions in the endothelium of thoracic aortas, whereas PARP inhibition decreased their expressions to control levels. Conclusion. Our results indicate that PARP activation in the vascular system may be a contributory factor to the impaired endothelial function associated with aldosterone administration. |
| first_indexed | 2024-03-07T17:43:50Z |
| format | Article |
| id | doaj.art-47bfd81741554e468cb0d6fde1c00083 |
| institution | Directory Open Access Journal |
| issn | 1470-3203 |
| language | English |
| last_indexed | 2024-03-07T17:43:50Z |
| publishDate | 2009-09-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-47bfd81741554e468cb0d6fde1c000832024-03-02T15:24:51ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32032009-09-011010.1177/1470320309343655Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activationArda TasatargilMerih TekcanCiler Celik-OzenciNazli Ece GungorBedriniam DalkiranIntroduction. The aim of this study was to investigate whether activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) contributes to the development of aldosterone-induced endothelial dysfunction and treatment with the potent PARP inhibitor 1,5-isoquinolinediol (3 mg/kg/day, i.p.) could prevent endothelial dysfunction caused by aldosterone. Methods. Infusion of subpressor doses of aldosterone with subcutaneously implanted mini-osmotic pumps (0.05 mg/kg/day) to rats for 21 days induced the development of endothelial dysfunction. In order to evaluate endothelial function, isometric tension studies were performed in response to acetylcholine and sodium nitroprusside.Additionally, PAR (the end product of activated PARP) and PARP-1 expressions in the endothelium of thoracic aortas were evaluated by immunohistochemistry. Results. There was a significant loss of endothelium-dependent vasodilatation in response to acetylcholine in aldosterone-infused rats. In animals treated with 1,5-isoquinolinediol, the effect of aldosterone on vascular responsiveness was less than the untreated groups. Immunohistochemical studies demonstrated that aldosterone administration increased PAR and PARP-1 expressions in the endothelium of thoracic aortas, whereas PARP inhibition decreased their expressions to control levels. Conclusion. Our results indicate that PARP activation in the vascular system may be a contributory factor to the impaired endothelial function associated with aldosterone administration.https://doi.org/10.1177/1470320309343655 |
| spellingShingle | Arda Tasatargil Merih Tekcan Ciler Celik-Ozenci Nazli Ece Gungor Bedriniam Dalkiran Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation Journal of the Renin-Angiotensin-Aldosterone System |
| title | Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation |
| title_full | Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation |
| title_fullStr | Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation |
| title_full_unstemmed | Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation |
| title_short | Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation |
| title_sort | aldosterone induced endothelial dysfunction of rat aorta role of poly adp ribose activation |
| url | https://doi.org/10.1177/1470320309343655 |
| work_keys_str_mv | AT ardatasatargil aldosteroneinducedendothelialdysfunctionofrataortaroleofpolyadpriboseactivation AT merihtekcan aldosteroneinducedendothelialdysfunctionofrataortaroleofpolyadpriboseactivation AT cilercelikozenci aldosteroneinducedendothelialdysfunctionofrataortaroleofpolyadpriboseactivation AT nazliecegungor aldosteroneinducedendothelialdysfunctionofrataortaroleofpolyadpriboseactivation AT bedriniamdalkiran aldosteroneinducedendothelialdysfunctionofrataortaroleofpolyadpriboseactivation |