Histone deacetylase (HDAC) inhibitors have shown beneficial effects in animal models of cardiovascular diseases. We hypothesized that HDAC inhibitor, sodium valproate (VPA), has cardiac and vascular protective effects in rats with pressure overload cardiac hypertrophy induced by transverse aortic constriction (TAC). Sections of the heart were visualized after hematoxylin and eosin staining, picrosirius red staining and immunohistochemistry. The expression of genes related to cardiac hypertrophy, fibrosis, and oxidative stress was determined by quantitative real-time polymerase chain reaction. The aortic ring tension analysis was conducted using both the ascending aorta and descending thoracic aorta. TAC increased the expression of hypertrophic, fibrotic, and oxidative stress genes, which was attenuated by VPA. In the ascending aorta with intact endothelium, there was a significant decrease in the relaxation response, which was recovered by VPA treatment. These results indicate that VPA has cardiac and vascular protective effects in rats with pressure overload cardiac hypertrophy.

• MeSH
• Aorta drug effects   physiopathology   surgery   MeSH
• Arterial Pressure drug effects   MeSH
• Fibrosis MeSH
• Ventricular Function, Left drug effects   MeSH
• Hypertrophy, Left Ventricular metabolism   pathology   physiopathology   prevention & control   MeSH
• Histone Deacetylase Inhibitors pharmacology   MeSH
• Valproic Acid pharmacology   MeSH
• Ligation MeSH
• Disease Models, Animal MeSH
• Myocardium metabolism   pathology   MeSH
• Oxidative Stress drug effects   MeSH
• Rats, Sprague-Dawley MeSH
• Gene Expression Regulation MeSH
• Ventricular Remodeling drug effects   MeSH
• Vasodilation drug effects   MeSH
• Vasodilator Agents pharmacology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Histone Deacetylase Inhibitors MeSH
• Valproic Acid MeSH
• Vasodilator Agents MeSH

We evaluated the time course of activation of endocardial endothelial cells and cardiomyocytes in adult rats with pressure overload induced by the abdominal aortic constriction. The silver staining technique for nucleolar organizer region was used to mark an increased transcriptional activity of the cells. An increased number of nucleoli was already detected in the endocardial endothelium of the left ventricle 5 h post-operatively, while the response of cardiomyocytes was still absent. Twenty-four h after constriction, the activation of the endocardial endothelium and cardiomyocytes was evident in both ventricles. A similar delay was observed between the nucleolar activation in vascular endothelium and smooth muscle cells of the abdominal aorta. In contrast, these cells of the thoracic aorta did not exhibit any significant increase of the transcriptional activity. The sequential stimulation of the transcriptional activity of the left ventricular endocardial endothelial cells and the subjacent cardiac myocytes due to pressure overload is in accord with the view that the endocardium may serve as a mechanotransducer which converts the hemodynamic changes into the signals that influence the growth of the cardiac myocytes.

• MeSH
• Aorta MeSH
• Endothelium, Vascular metabolism   MeSH
• Endocardium cytology   metabolism   MeSH
• Transcription, Genetic MeSH
• Constriction MeSH
• Blood Pressure * MeSH
• Rats MeSH
• Myocardium cytology   metabolism   MeSH
• Nucleolus Organizer Region metabolism   MeSH
• Rats, Wistar MeSH
• Muscle, Smooth, Vascular cytology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH