Sodium valproate treatment reverses endothelial dysfunction in aorta from rabbits with acute myocardial infarction.
In: European Journal of Pharmacology, Jg. 970 (2024-05-05), S. N.PAG
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Zugriff:
Sodium valproate (VPA), a histone deacetylase (HDAC) inhibitor, could be a promising candidate to treat acute myocardial infarction (AMI). In this study, AMI was induced in New Zealand White rabbits by occluding the left circumflex coronary artery for 1 h, followed by reperfusion. The animals were distributed into three experimental groups: the sham-operated group (SHAM), the AMI group and the AMI + VPA group (AMI treated with VPA 500 mg/kg/day). After 5 weeks, abdominal aorta was removed and used for isometric recording of tension in organ baths or protein expression by Western blot, and plasma for the determination of nitrate/nitrite (NOx) levels by colorimetric assay. Our results indicated that AMI induced a reduction of the endothelium-dependent response to acetylcholine without modifying the endothelium-independent response to sodium nitroprusside, leading to endothelial dysfunction. VPA treatment reversed AMI-induced endothelial dysfunction and even increased NO sensitivity in vascular smooth muscle. This response was consistent with an antioxidant effect of VPA, as it was able to reverse the superoxide dismutase 1 (SOD 1) down-regulation induced by AMI. Our experiments also ruled out that the VPA mechanism was related to eNOS, iNOS, sGC and arginase expression or changes in NOx plasma levels. Therefore, we conclude that VPA improves vasodilation by increasing NO bioavailability, likely due to its antioxidant effect. Since endothelial dysfunction was closely related to AMI, VPA treatment could increase aortic blood flow, making it a potential agent in reperfusion therapy that can prevent the vascular damage. [Display omitted] • VPA treatment reverses AMI-induced endothelial dysfunction in rabbit aorta. • VPA increases NO bioavailability in response to acetylcholine. • VPA mechanism is independent of eNOS-sGC, iNOS or arginase protein expression. • AMI decreases SOD1 protein expression in aorta. • Enhancement of VPA in AMI may be related to the ability to restore SOD1. [ABSTRACT FROM AUTHOR]
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Sodium valproate treatment reverses endothelial dysfunction in aorta from rabbits with acute myocardial infarction.
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Autor/in / Beteiligte Person: | Guerra-Ojeda, Sol ; Suarez, Andrea ; Belmonte, Begoña ; Marchio, Patricia ; Genovés, Patricia ; Arias, Oscar Julian ; Aldasoro, Martin ; Vila, José M. ; Serna, Eva ; Mauricio, Maria D. |
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Zeitschrift: | European Journal of Pharmacology, Jg. 970 (2024-05-05), S. N.PAG |
Veröffentlichung: | 2024 |
Medientyp: | academicJournal |
ISSN: | 0014-2999 (print) |
DOI: | 10.1016/j.ejphar.2024.176475 |
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