Effect of β-Adrenoceptor Blockers on Sarcoplasmic Reticular Function and Gene Expression in the Ischemic-Reperfused Heart

• Published in: The Journal of pharmacology and experimental therapeutics 2000-04, Vol.293 (1), p.15
• Main Authors: Rana M. Temsah, Chadwyn Dyck, Thomas Netticadan, Donald Chapman, Vijayan Elimban, Naranjan S. Dhalla
• Format: Article
• Language: English
• ISSN: 0022-3565; 1521-0103

Although β-adrenoceptor (β-AR) blockers are used for the treatment of ischemic heart disease, the mechanisms of their beneficial actions have not been fully elucidated. In view of the role of sarcoplasmic reticular (SR) abnormalities in cardiac dysfunction due to ischemia-reperfusion (I/R), we examined the effects of β-AR blockers on the I/R-induced changes in SR Ca 2+ uptake and release, as well as the protein contents and gene expression of ryanodine receptor, SR Ca 2+ -pump, phospholamban, and calsequestrin. I/R in isolated rat hearts was induced by stopping the perfusion for 30 min and then reperfusing the ischemic hearts for 60 min. Hearts were treated with or without 10 μM atenolol, a β 1 -specific blocker, or 10 μM propranolol, a nonspecific β-blocker, 10 min before inducing ischemia as well as during the reperfusion period. I/R depressed cardiac performance, SR Ca 2+ uptake, and Ca 2+ release activities, protein contents, as well as Ca 2+ /calmodulin-dependent protein kinase and cAMP-dependent protein kinase-mediated phosphorylations, significantly. The mRNA levels for SR Ca 2+ pump, ryanodine receptors, phospholamban, and calsequestrin were also reduced by I/R. All these changes due to I/R were partially prevented by β-AR blocker treatment. The results indicate that the beneficial effects of β-AR blockers on cardiac performance in the I/R hearts may be related to the prevention of changes in SR Ca 2+ uptake and release activities, protein contents, as well as Ca 2+ /calmodulin-dependent protein kinase and cAMP-dependent protein kinase phosphorylations of SR proteins. On the other hand, the protection of I/R-induced alterations in mRNA levels for SR proteins by β-AR blockers suggests cardiac SR gene expression as a molecular site of their cardioprotective action.