Serial changes in sarcoplasmic reticulum gene expression in volume-overloaded cardiac hypertrophy in the rat: effect of an angiotensin II receptor antagonist
| Autor: | Mareomi Hamada, Hidetoshi Hashida, Kunio Hiwada |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty SERCA medicine.drug_class Gene Expression Tetrazoles Calcium-Transporting ATPases Biology Calsequestrin Ryanodine receptor 2 Ventricular Function Left Muscle hypertrophy Rats Sprague-Dawley Angiotensin Receptor Antagonists Internal medicine medicine Animals RNA Messenger Ryanodine receptor Angiotensin II Biphenyl Compounds Calcium-Binding Proteins Ryanodine Receptor Calcium Release Channel General Medicine Receptor antagonist Blotting Northern Phospholamban Rats Sarcoplasmic Reticulum Endocrinology cardiovascular system Benzimidazoles Hypertrophy Left Ventricular |
| Zdroj: | Clinical Science. 96:387-395 |
| ISSN: | 1470-8736 0143-5221 |
| Popis: | This study was designed to clarify whether gene expression in the cardiac sarcoplasmic reticulum [sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban, ryanodine receptor and calsequestrin] changes in accordance with left ventricular functional alterations in the volume-overloaded heart. Further, the effect of the angiotensin II type 1 receptor antagonist, TCV-116, on the expression of these genes was also evaluated. Left ventricular fractional shortening was significantly increased at 7 days, had returned to control levels at 21 days, and had significantly decreased at 35 days after the shunt operation, compared with sham-operated rats. The level of SERCA mRNA was significantly decreased at both 21 days and 35 days after the shunt operation. The levels of ryanodine receptor and phospholamban mRNAs were significantly decreased at 35 days in shunt-operated rats. The decrease in the SERCA mRNA level preceded the development of cardiac dysfunction. The levels of SERCA and ryanodine receptor mRNAs were correlated positively with left ventricular fractional shortening (r = 0.73, P< 0.0001 and r = 0.61, P< 0.01 respectively). Attenuation of the decrease in left ventricular fractional shortening occurred on treatment with TCV-116. After the treatment with TCV-116, the levels of SERCA and phospholamban mRNAs were restored to the respective values in sham-operated rats. Ryanodine receptor mRNA levels remained unchanged after treatment with TCV-116. These results indicate that the down-regulation of SERCA and ryanodine receptor mRNA levels may be related to cardiac dysfunction in the volume-overloaded heart. In addition, treatment with an angiotensin II receptor antagonist may restore the altered sarcoplasmic reticulum mRNA levels to control levels, and this may result in attenuation of the functional impairment in the volume-overloaded heart. |
| Databáze: | OpenAIRE |
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